Campus Connections

New Connections (Posted September 1, 2010)...

Targeted Drug Leads to Regression of Metastatic Melanoma

Use of an experimental targeted drug to treat metastatic melanoma tumors with a specific genetic signature was successful in more than 80 percent of patients in a Phase I clinical trial. Results of the trial of PLX4032, an inhibitor of a protein called BRAF that is overactive in more than half of all melanomas, appear in the August 26 New England Journal of Medicine. Keith Flaherty, MD, director of Developmental Therapeutics at the Massachusetts General Hospital Cancer Center, member of the Harvard Medical School faculty, and lead and corresponding author of the article, says, "Until now, available therapies were few and unreliable, so these findings can really change the outlook for patients whose tumors are fueled by this mutation." Flaherty, formerly at the University of Pennsylvania Abramson Cancer Center, began to explore whether drugs targeting the mutation might interfere with tumor growth nearly a decade ago. After one potential drug was not effective, he began working in collaboration with Paul Chapman, MD, of Memorial Sloan-Kettering Cancer Center in New York to study PLX4032, an agent developed by Plexxikon and licensed to Roche Pharmaceuticals. Initial trial results were disappointing, but a new formulation that increased the bioavailability of PLX4032 proved to have rapid results that are being reported in the new paper. The initial stage of the study--led by Flaherty, Chapman, and colleagues at six sites in the U.S. and Australia--was designed to establish the effective dose. It enrolled 55 cancer patients, most with metastatic melanoma, who received escalating doses of PLX4032 until unacceptable side effects occurred. BRAF mutations were present in the melanomas of 16 participants in the latter part of this stage, and in 11 of those patients, tumors quickly shrank or, in one instance, disappeared. Three participants with BRAF-mutated thyroid cancers also had their tumors shrink or stabilize in response to PLX4032 treatment. The second stage enrolled 32 patients with BRAF-mutated melanoma who received the PLX4032 dosage established in the first phase: 960 mg twice a day. In 26 of those participants, tumors shrank more than 30 percent, meeting the criteria for clinical response, and completely disappeared in two. Since another two participants had some reduction in the size of their tumors, Flaherty projects that PLX4032 appears to shrink tumors in approximately 90 percent of patients with BRAF-mutated melanomas. As seen in trials of other targeted cancer treatments, resistance to PLX4032 developed in the tumors of many participants, leading to resumed tumor growth. Currently tumor suppression has been maintained from about three months to longer than two years, with an average progression-free survival of eight months, and follow-up studies are exploring how resistance occurs and potential strategies to get around it. Two additional MGH-based clinical trials are now under way--a Phase II study in patients unsuccessfully treated with drugs already approved by the Food and Drug Administration, enrollment for which is complete, and a larger Phase III study that compares PLX4032 with dacarbazine in newly diagnosed patients. The newly published study was funded by Plexxikon and Roche. Source: EurekAlert! 8/25/10

Clinical Trial Findings Challenge Clinical Practice

Patients with coronary artery disease undergoing angioplasty do not benefit from having their circulation artificially supported with a balloon pump as a preventative measure during angioplasty, according to the first randomized trial studying the practice, published in August in the Journal of the American Medical Association. The trial was carried out across 17 tertiary referral cardiac centres in the United Kingdom and was designed and led by Drs. Divaka Perera and Simon Redwood, interventional cardiologists at Guy's and St Thomas' Foundation Trust in London. The study was funded by unrestricted educational grants and the principal investigators were supported by the atherosclerosis theme of the National Institute for Health Research comprehensive Biomedical Research Centre at Guy's and St Thomas' and King's College London. Patients with poor heart function and extensively narrowed heart arteries are at higher risk of complications following angioplasty, and there has been much interest in the balloon pump as a means of reducing such adverse events. When a balloon pump is used, it is placed inside the patient's aorta to provide circulatory support to their failing hearts. Over the last 20 years, cardiologists across the world have adopted use of the balloon pump as a preventative measure during high-risk angioplasty, but this common practice has been based on anecdotal accounts and small observational studies, which are limited by selection bias. The Balloon pump assisted Coronary Intervention Study (BCIS-1) involved 301 patients with severe left ventricular dysfunction and extensive coronary artery disease. They were randomly assigned to either have the balloon pump inserted before angioplasty or to have angioplasty without planned balloon pump support. There was no difference in the proportion of patients who suffered major cardiovascular complications (comprising death, acute myocardial infarction, cerebrovascular events, or further revascularisation, at hospital discharge capped at 28 days) in the group who received a balloon pump beforehand (15.2 percent), compared to those who did not (16 percent). However, approximately one in eight of the latter group required an emergency balloon pump insertion during the procedure, emphasizing the importance of having a balloon pump on standby when undertaking such cases. The study findings raise important questions about current clinical practice, and whether it is necessary to use a balloon pump routinely during the procedure. The findings may reflect the fact that angioplasty has become a less risky procedure over time, as cardiologists have increased their skills. Seventeen hospitals recruited patients into this study; more than half of the patients were recruited into the study at St Thomas' Hospital, Birmingham Heartlands Hospital, Brighton and Sussex University Hospital, Leeds Teaching Hospitals, and Liverpool Heart and Chest Hospital. Source: EurekAlert! 8/24/10

Earlier Connections...

College of Medicine Receives $54 Million Grant for Asthma Research

The Penn State College of Medicine's Department of Public Health Sciences has received a grant of about $54 million over seven years to act as the data coordinating center for the National Heart Lung and Blood Institute's (NHLBI's) AsthmaNet. This grant is one of the largest in the college's history. AsthmaNet is a research collaboration of multiple clinical centers across the nation that conducts clinical trials to address new treatments and asthma management. The NHLBI Asthma Network will develop and conduct multiple clinical trials to address the most important asthma management questions and new treatment approaches in pediatric and adult populations. "The emphasis will be on Phase II and Phase III clinical trials that help identify optimal therapies for a variety of asthma phenotypes, genotypes, and racial and ethnic backgrounds," said Dave Mauger, the study's principal investigator and division chief of biostatistics in Public Health Sciences. Source: EurekAlert! 8/11/10 

Clinical Research Network Launched for Baltimore Region

The Johns Hopkins Institute for Clinical and Translational Research, in collaboration with Anne Arundel Health System and the Greater Baltimore Medical Center, has established a new network of academic and community-based clinical researchers, the Johns Hopkins Clinical Research Network (JHCRN). The JHCRN, which will provide new opportunities for research collaborations, is designed to accelerate the transfer of new diagnostic, treatment, and disease prevention advances from the research arena to patient care. The JHCRN creates a bridge for research between Hopkins and community-based medical centers by linking physician-scientists and staff from the Johns Hopkins Medical Institutions with community-based medical centers in the region. The network, which will ultimately have additional member institutions, will serve several purposes, the most important of which is to make clinical trials available to patients who may not ordinarily have access to them. The JHCRN directly addresses the many complexities of conducting multisite and multi-institutional trials by providing investigators with a larger patient pool and a seamless platform that uses common research protocols. The goal of the network is to speed the approval of new trials while ensuring careful oversight of patient safety. Rapid start-up and timely completion of research studies, aided by widespread access to the clinical trials, will make promising therapies available for patient use more quickly. Source: Johns Hopkins 8/11/10 

$600,000 Award to Support Gene Therapy Study on Duchenne

Parent Project Muscular Dystrophy (PPMD), the largest nonprofit organization in the United States focused on finding a cure for Duchenne muscular dystrophy (Duchenne), announced that PPMD will award a $600,000 grant to Nationwide Children's Hospital in Columbus, Ohio to conduct clinical testing of a promising gene therapy technique for muscle disease. Investigators, led by Jerry Mendell, MD, director of the Center for Gene Therapy in the Research Institute at Nationwide Children's Hospital, with coinvestigator Brian Kaspar, PhD, will inject a modified virus (vector) carrying the gene for the muscle growth-stimulating protein follistatin into the quadriceps muscles of volunteers with Becker muscular dystrophy and sporadic inclusion body myositis. The goal of the study is to verify that the procedure is safe and to document any increase in quadriceps muscle size and function. If the initial study is successful, the investigators will expand the research to a Phase II study and will also make plans to test it in Duchenne muscular dystrophy and other muscle diseases. The first clinical studies are planned to start in early 2011. This grant was made possible, in large, part due to the generosity of Chris and Anna Stansbury and Robert H. Book. Source: EurekAlert! 8/10/10 

Clinical Trial of NIH-Developed Dengue Vaccine Begins

After more than a decade of development at the National Institutes of Health (NIH), a vaccine to prevent infection by the mosquito-borne dengue virus has begun human clinical testing. The vaccine was developed by scientists at the National Institute of Allergy and Infectious Diseases (NIAID) and is undergoing clinical study at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Md. Dengue fever is caused by any of four related viruses — DENV-1, DENV-2, DENV-3 and DENV-4 — which are transmitted to humans by Aedes mosquitoes. Dengue virus is prevalent in the tropical and subtropical regions of the world and each year infects about 50 million to 100 million people. It accounts for 25,000 deaths annually; most of them in children. The new vaccine is tetravalent, meaning that it is designed to protect against all four dengue viruses. To optimize the immune response to each dengue serotype, the researchers are testing three different candidate combinations of the four monovalent vaccines. In this Phase I trial, study volunteers who have never been exposed to dengue were randomly assigned to receive one of the candidate tetravalent vaccine formulations or a placebo. The candidate vaccines are live-attenuated, or created by making the live virus harmless or less virulent. Evaluation of a second candidate combination vaccine has been initiated at the University of Vermont in Burlington, and trials of the third candidate will begin shortly thereafter at Johns Hopkins. After determining which tetravalent vaccine is most promising, the researchers will test that candidate in a trial in a new group of volunteers in Brazil, where dengue has become highly prevalent. The next stage of testing, a Phase II trial, will involve more participants and will test for differences in preliminary signs of effectiveness between people who have been exposed to dengue and those who have not, as well as the need for a booster shot within a few months of the initial vaccination. Source: NIH 8/9/10 

Expectations May Affect Placebo Response in Patients With Parkinson’s Disease

Individuals with Parkinson’s disease were more likely to have a neurochemical response to a placebo medication if they were told they had higher odds of receiving an active drug, according to a report in the August issue of Archives of General Psychiatry. “The promise of symptom improvement that is elicited by a placebo is a powerful modulator of brain neurochemistry,” the authors write as background information in the article. “Understanding the factors that modify the strength of the placebo effect is of major clinical as well as fundamental scientific significance.” In patients with Parkinson’s disease, the expectation of symptom improvement is associated with the release of the neurotransmitter dopamine, and the manipulation of this expectation has been shown to affect the motor performance of patients with the condition. Sarah C. Lidstone, PhD, of Pacific Parkinson’s Research Centre at Vancouver Coastal Health and the University of British Columbia, Vancouver, Canada, and colleagues studied 35 patients with mild to moderate Parkinson’s disease undergoing treatment with the medication levodopa. On the first day of the study, a baseline positron emission tomographic scan was performed, participants were given levodopa and a second scan was performed one hour later to assess dopamine response. On the second day, patients were randomly assigned to one of four groups, during which they were told they had either a 25 percent, 50 percent, 75 percent, or 100 percent chance of receiving active medication before the third scan; however, all patients were given placebo. Patients who were told they had a 75 percent chance of receiving active medication demonstrated a significant release of dopamine in response to the placebo, whereas those in the other groups did not. Patients’ reactions to the active medication before the first scan was also correlated with their response to placebo. “Our findings may have important implications for the design of clinical trials, as we have shown that both the probability of receiving active treatment—which varies in clinical trials depending on the study design and the information provided to the patient—as well as the treatment history of the patient influence dopamine system activity and consequently clinical outcome,” the authors conclude. This study was funded by the Michael Smith Foundation for Health Research, the Canadian Institutes for Health Research, and a TRIUMF Life Sciences Grant. Source: Newswise 8/2/10 

Research Center Receives $3.2 Million Grant for Comparative Effectiveness Research

The NYU Health Promotion and Prevention Research Center (NYU PRC) at the NYU School of Medicine announced it has received a $3.2 million award from the Centers for Disease Control and Prevention (CDC) to establish a Comparative Effectiveness Research Program focused on hypertension and colorectal cancer health disparities in African-American men in New York City. The NYU PRC is one of only four of the 37 PRC research facilities nationwide to receive this prestigious award. The program will build upon the center’s commitment to build and enhance community capacity for health promotion and disease prevention across diverse populations in New York City. The NYU PRC’s mission is to bring together the unique talents of faculty and staff across several institutions, along with a wide variety of community partners, to accelerate improvements in population health. To achieve this goal, the NYU PRC conducts a core research project to develop, implement, and test community health-worker programs for diabetes prevention in diverse communities of New York City. NYU PRC’s core research project, titled Project RICE (Reaching Immigrants Through Community Empowerment), aims to reduce diabetes in recent Asian-American immigrants to New York City. Source: Newswise 8/2/10 

Plant Compound Resveratrol Shown to Suppresses Inflammation, Free Radicals in Humans

Resveratrol, a popular plant extract shown to prolong life in yeast and lower animals due to its anti-inflammatory and antioxidant properties, appears also to suppress inflammation in humans, based on results from the first prospective human trial of the extract conducted by University at Buffalo endocrinologists. Results of the study appear as a rapid electronic publication on the Journal of Clinical Endocrinology & Metabolism website, and will be published in an upcoming print issue of the journal. The paper also has been selected for inclusion in Translational Research in Endocrinology & Metabolism, a new online anthology that highlights the latest clinical applications of cutting-edge research from the journals of the Endocrine Society. Resveratrol is a compound produced naturally by several plants when under attack by pathogens such as bacteria or fungi, and is found in the skin of red grapes and in red wine. It also is produced by chemical synthesis derived primarily from Japanese knotweed and is sold as a nutritional supplement. Husam Ghanim, PhD, research assistant professor of medicine and first author on the study, notes that resveratrol has been shown to prolong life and to reduce the rate of aging in yeast, roundworms, and fruit flies, actions thought to be affected by increased expression of a particular gene associated with longevity. The compound also is thought to play a role in insulin resistance, a condition related to oxidative stress, which has a significant detrimental effect on overall health. "Since there are no data demonstrating the effect of resveratrol on oxidative and inflammatory stress in humans," says Paresh Dandona, MD, PhD, distinguished professor of medicine and senior author on the study, "we decided to determine if the compound reduces the level of oxidative and inflammatory stress in humans. Several of the key mediators of insulin resistance also are pro-inflammatory, so we investigated the effect of resveratrol on their expression, as well." The study was conducted at Kaleida Health's Diabetes-Endocrinology Center of Western New York, which Dandona directs. A nutritional supplement containing 40 milligrams of resveratrol was used as the active product. Twenty participants were randomized into two groups of 10: one group received the supplement, while the other group received an identical pill containing no active ingredient. Participants took the pill once a day for six weeks. Fasting blood samples were collected as the start of the trial and at weeks one, three, and six. Results showed that resveratrol suppressed the generation of free radicals, or reactive oxygen species, unstable molecules known to cause oxidative stress and release proinflammatory factors into the blood stream, resulting in damage to the blood vessel lining. Blood samples from persons taking resveratrol also showed suppression of the inflammatory protein tumor necrosis factor and other similar compounds that increase inflammation in blood vessels and interfere with insulin action, causing insulin resistance and the risk of developing diabetes. While these results are promising, Dandona added a caveat: The study did not eliminate the possibility that something in the extract other than resveratrol was responsible for the anti-inflammatory effects. The study was supported in part by grants to Dandona from the National Institutes of Health and the American Diabetes Association. Source: EurekAlert! 7/29/10 

Medical Center Recognized for High Standards in Protecting the Welfare of Research Participants

Cedars-Sinai Medical Center has received its third consecutive full accreditation from the Association for the Accreditation of Human Research Protection Programs, Inc. (AAHRPP), whose goal is to ensure that research institutions meet the highest standards in respecting and protecting individuals who participate in research. This is done through a rigorous review process that accredits only those organizations that rigorously demonstrate tangible evidence—through policies, procedures, and practices—of their commitment to scientifically and ethically safe and sound research, and to continuous improvement. Cedars-Sinai was the first organization to be accredited in California, receiving full accreditation in April 2004. At the end of the initial three-year period, the medical center received its second full accreditation in 2007. The new accreditation is now effective for five years. In certifying Cedars-Sinai’s most recent accreditation, AAHRPP highlighted many strengths of the medical center’s protection program, including ongoing educational programs for Cedars-Sinai researchers that focused on the importance of protecting research participants, a comprehensive quality assurance and monitoring process, and extensive staff support to ensure the highest quality informed consent process for research subjects. Source: Newswise 7/23/10 

Sickle Cell Treatment Enters Phase III Clinical Trial

An experimental treatment for sickle cell disease developed at the Los Angeles Biomedical Research Institute (LA BioMed) has entered Phase III clinical trials, David I. Meyer, PhD, LA BioMed president and CEO, announced in July. Researchers throughout the U.S. have begun administering the sickle cell treatment developed by investigators led by Yutaka Niihara, MD, MPH, at LA BioMed, and licensed to Emmaus Medical, Inc. The patented drug treatment involves the oral administration of L-glutamine, which is the most common amino acid in the body. This is one of a very few experimental treatments for sickle cell disease to reach the Phase III clinical trial stage. "As a physician, I have seen firsthand the severe pain in patients with sickle cell disease, so I am very pleased we have reached this stage in our development of this potential treatment," said Dr. Niihara. "In the Phase II clinical trial, we observed an excellent safety profile and positive trends in decreasing the number of crises as well as reducing the frequency of hospitalizations in sickle cell disease patients. We look forward to the findings from the much larger group of research volunteers we will be seeking in the Phase III clinical trial." In the new trial, researchers at 20 to 25 sites around the country will be seeking up to 225 research volunteers, age 5 years and older, with a diagnosis of sickle cell anemia or sickle beta O-thalassemia who have a history of at least two episodes of painful crisis during the past 12 months. The trial is a 53-week study requiring monthly visits to the research facility. It is funded by Emmaus Medical. Source: EurekAlert! 7/23/10 

A New Drug Treatment Hopes to Close the Window on Colon Cancer

Cancer surgery wreaks havoc on a body's immune system and stress hormones exacerbate the problem. As a result, about half of those who undergo surgery for tumor removal experience a recurrence of cancer in the same region or other parts of the body. A new clinical approach being developed and tested by Tel Aviv University researchers may be the key to making cancer operations more successful. Prof. Shamgar Ben-Eliyahu, head of Tel Aviv University's Department of Psychology, has opened on a new frontier in cancer research: he is recruiting colon cancer patients for a new clinical study that will test a cocktail of drugs to prevent the negative effects of stress responses to surgery. If successful, it will help the immune system maintain its vigor and prevent the occurrence of new tumors. Prof. Ben-Eliyahu described his method in a recent issue of the Journal of Immunology; he and other research teams have confirmed that a competent immune system is critical before, during, and after surgery for tumor removal. However, stress responses of the body during this period jeopardize immune competence and facilitate tumor metastasis. Combining two widely known medications that affect immune and stress responses, Prof. Ben-Eliyahu has developed a formula he hopes will keep an immune system strong and prevent the recurrence of cancer. Already tested in animal models, the compounds will be employed in a clinical trial in Israel, for which Prof. Ben-Eliyahu's team is currently recruiting patients and funds. They hope to have 800 colon cancer patients participate in the 20-day trial, due to begin shortly. The two compounds to be used in the study are a beta-adrenergic antagonist, which is used to treat hypertension and anxiety, and a Cyclooxygenase-2 inhibitor, used against inflammation and pain. Since the two drugs are already widely available and routinely used in the clinical setting, no patents need be filed for the application of these drugs. Source: EurekAlert! 7/21/10 

Potential New Sickle Cell Treatment to be Investigated

Researchers from the La Jolla Institute for Allergy & Immunology have joined forces with the Dana-Farber Cancer Institute in Boston, Mass., and Washington University in St. Louis, Mo., to investigate a potential new therapy for sickle cell disease, a severe and chronic illness affecting more than 70,000 Americans and several million people worldwide. A drug called Lexiscan™ (regadenoson from Astellas Pharma US, Inc.), approved by the Food and Drug Administration as a pharmacologic stress agent used to diagnose heart disease in some patients, will be tested in the multicenter clinical trial. Patient recruitment for the trial is under way. "We will be testing the ability of Lexiscan to reduce inflammation that contributes to the poor blood flow and serious complications characteristic of sickle cell disease," said the La Jolla Institute's Joel Linden, PhD, whose research laid the groundwork for the trial. "We are hopeful that this therapy will prove important in improving and extending the lives of sickle cell patients." The trial is being funded primarily by a $1.2 million, two-year American Recovery and Reinvestment Act stimulus grant from the National Heart Lung and Blood Institute, part of the National Institutes of Health. Dr. Linden and David G. Nathan, MD, president emeritus of the Dana-Farber Cancer Institute, former physician-in-chief at Children's Hospital Boston, and one of the world's top sickle cell experts, are coinvestigators leading the project. To ensure that the drug does not cause toxicity, Dr. Linden and his team at the La Jolla Institute will first analyze blood samples from adult participants with sickle cell disease but no painful crises receiving different test doses of Lexiscan. Pending these results, the team will then move to test Lexiscan in adults with pain crises and acute chest syndrome, and, in the second year, in children age 14 and older. Source: EurekAlert! 7/20/10 

FDA Accepts Historical Controls for Epilepsy Monotherapy Studies

New York University researchers revealed that data from previously completed withdrawal to monotherapy studies for antiepileptic drugs (AEDs) provide a valid control for future studies, obviating the need for placebo/pseudo-placebo trials to demonstrate the efficacy of these drugs as monotherapy. Results of this study are now available online in Epilepsia. According to a National Institute of Neurological Disorders and Stroke workshop, monotherapy is the ultimate treatment strategy for newly diagnosed and many long-term epilepsy patients, because of fewer side effects, better compliance, less risk of fetal malformations (teratogencity), and lower cost compared to polytherapy. However, in the U.S., it is difficult to get monotherapy approval for AEDs because the Food and Drug Administration (FDA), in accordance with the International Conference on Harmonization (ICH), requires an internal, interpretable control group in which the test drug shows superiority over the control. New AEDs, while offering improvements in safety and efficacy, rarely demonstrate superiority compared to standard AEDs, leaving placebo or pseudo-placebo as the only acceptable internal controls. The pseudo-placebo withdrawal to monotherapy study model assigns treatment-resistant patients to receive a study drug or a suboptimal maintenance dose of a safe and effective active drug. Once patients are randomized and standardized to the intended dose, they undergo a withdrawal phase (when background AEDs are removed over a specified time frame) followed by a monotherapy phase. The trial continues until either all phases are completed or patients reach prespecified endpoints. Study leader Dr. Jacqueline French explains why this clinical trial model is not suited for epilepsy patients: "Epilepsy is different from other conditions where placebo may be utilized (such as hypertension), since there is no way to exit a patient at a warning stage, before harm can occur. In a hypertensive patient, one can withdraw a patient on placebo if blood pressure increases, before it gets dangerously high. But with an epilepsy patient, the escape criteria consist of an increase or worsening of seizures, which by itself can be considered an adverse outcome." The study authors proposed that a historical control, based on an evaluation of prior pseudo-placebo withdrawal to monotherapy studies, would provide a valid alternative to an actual control group. The team analyzed eight separate studies of similar design and escape criteria, with randomized patients of common demographic characteristics. The primary endpoint was the same for all trials: percent of patients exiting the trial due to seizure worsening. All eight studies had consistent outcomes, with the percentages of patients exiting their respective trials ranging from 74.9 percent to 95.9 percent. Dr. French concludes, "These trials would appear to meet the criteria set forth by ICH for use of historical control. Therefore, this group of trials might reasonably be used as historical controls for future trials of withdrawal to monotherapy using a similar design in a similar population." The historical control design allows all patients to receive a promising AED at an effective dose, making the study more attractive to patients and to physicians. Based on this study, the FDA has accepted the concept of historical controls in this setting, a major milestone in AED development. Several trials utilizing this design planned for regulatory submission have begun. Source: EurekAlert! 7/20/10 

NIH Funds International Centers of Excellence for Malaria Research

In an effort to accelerate the control of malaria and help eliminate it worldwide, the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (NIH), in July announced approximately $14 million in first-year funding to establish 10 new malaria research centers around the world. The seven-year awards will establish the International Centers of Excellence for Malaria Research (ICEMRs) in regions where malaria is endemic, including parts of Africa, Asia, the Pacific Islands, and Latin America. These regions include some of the focus countries of the President's Malaria Initiative, an effort that since 2005 has worked to fight malaria in the regions most affected by the disease. Teams of scientists involved in the ICEMR program will be conducting research in more than 20 countries. The centers will integrate clinical and field approaches with laboratory-based immunologic, molecular, and genomic methods. They will adapt their research to changes in malaria epidemiology and emerging research needs as well as opportunities within the specific regions. Their findings are expected to help inform how new interventions and control strategies are designed and evaluated in the future. Principal investigators selected to establish ICEMRs at Johns Hopkins University, Baltimore, Md.; New York University School of Medicine, New York City; Pennsylvania State University, University Park; University of California, San Francisco; Caucaseo Scientific Research Center, Cali, Colombia; Case Western Reserve University, Cleveland, Ohio; Tulane University, New Orleans, La.; University of Washington, Seattle; Michigan State University, East Lansing; and University of California, San Diego. Source: EurekAlert! 7/8/10 

First U.S. Surgery to Compare NOTES to Laparoscopy

As part of the only U.S. prospective multicenter clinical trial to compare natural orifice translumenal endoscopic surgery (NOTES) to laparoscopy, surgeons at the University of California, San Diego (UCSD) School of Medicine have performed the trial's first oral gallbladder removal. This landmark study will evaluate whether or not NOTES is safe and as effective as traditional laparoscopic surgery. "This groundbreaking study is the first in the world to compare oral and transvaginal NOTES to traditional laparoscopy," said Santiago Horgan, MD, principal investigator of the UCSD study site and chief of minimally invasive surgery at UC San Diego Health System. This study uses the mouth and vagina as routes to the gallbladder. Rather than creating up to five incisions in the abdominal wall, tools are passed down the mouth and through a hole created in the stomach (transgastric) or through the vagina (transvaginal). Under this clinical trial protocol, a laparoscopic port is required. Horgan opted to make two tiny incisions, requiring no stitches, to pass a camera and to inflate the abdomen for optimal safety and visibility. The actual gallbladder removal was performed entirely through the mouth. "What is unique about this trial is that we will not only evaluate the safety and efficacy of NOTES compared to laparoscopy, but will also assess and compare pain levels, cosmetic outcomes, operative costs and logistical outcomes," said Horgan, who has performed more than 70 NOTES surgeries. On a randomized basis, up to 200 patients will be enrolled in the clinical trial to obtain 70 NOTES cases (35 transgastric and 35 transvaginal) and 70 laparoscopic cases. The UCSD site plans to enroll 20 patients. This trial is sponsored by the Natural Orifice Surgery Consortium for Assessment and Research, which represents the Society of American Gastrointestinal and Endoscopic Surgeons and the American Society for Gastrointestinal Endoscopy. Source: EurekAlert! 7/7/10 

University Launches Trial of New Multiple Sclerosis Treatment

Medical researchers led by a team from the University at Buffalo Department of Neurosurgery will embark on a landmark prospective, randomized, double-blinded study to test the safety and efficacy of interventional endovascular therapy--dubbed "liberation treatment"--on the symptoms and progression of multiple sclerosis (MS). Recent research has strongly associated chronic cerebrospinal venous insufficiency (CCSVI) with MS. It is hypothesized that the narrowing in the large veins in the neck and chest might cause improper drainage of blood from the brain, resulting in eventual injury to brain tissue. It is thought that angioplasty--treatment commonly used by cardiologists and other endovascular surgeons to treat atherosclerosis--may remedy the blockages. Now, researchers at the University at Buffalo will launch PREMiSe (Prospective Randomized Endovascular therapy in Multiple Sclerosis), a study to determine if endovascular intervention via balloon angioplasty to correct the blockages improves MS symptoms or progression. PREMiSe is believed to be the first study of its type being performed with institutional review board (IRB) approval in a rigorous fashion in the U.S. The study is led by principal investigator Adnan Siddiqui, MD, assistant professor of neurosurgery, with coprincipal investigators Elad Levy, MD, associate professor, and L.N. Hopkins, MD, professor and chair of the Department of Neurosurgery. Additional independent researchers from University at Buffalo will participate in the evaluation and follow-up of study patients. An independent data safety monitoring board will ensure the safety and effectiveness of the study on an ongoing basis. In the first phase of the study, 10 MS patients from the United States and Canada who exhibit venous insufficiency will undergo minimally invasive venous angioplasties to determine if the procedure can be performed safely. In its second phase, the study will randomize 20 MS patients to undergo either venous angioplasty or a "sham angioplasty" (i.e., a catheter will be inserted, but there will be no inflation of the balloon). The treatment will be blinded in such a way that neither the patient undergoing the procedure nor the clinicians evaluating the patient will be aware which procedure was performed. If results suggest an appropriate safety profile and preliminary effectiveness, researchers will approach the University at Buffalo IRB for an extension of the protocol to study a larger number of patients in order to convincingly prove or disprove a causal relationship between CCSVI and MS. Source: EurekAlert! 6/30/10 

Linguistics Professor Examines Manufacturers' Prescription Drug Websites

Lewis Glinert, a professor of linguistics at Dartmouth, and Jon Schommer, the associate head of the Department of Pharmaceutical Care and Health Systems at the University of Minnesota, have examined the corporate websites dedicated to the 100 best-selling prescription drugs. They found a startling lack of consistency in an industry where advertising standards are regulated by the Food and Drug Administration (FDA). "Communicating via a website is common practice today," says Glinert, "and consumers are very savvy about doing their own research on the Internet. The FDA has rules about direct-to-consumer print and television drug advertising, so we think it makes sense to also regulate websites and other marketing tools when it comes to prescription medicine. Consumers need consistent and balanced information." Glinert presented the study at the Communication, Medicine, and Ethics (COMET) 2010 Conference at Boston University School of Public Health in late June. Glinert and Schommer have previously published on the topic of direct-to-consumer drug advertising and Glinert has also presented their research at an FDA hearing. In this paper, Glinert and Schommer found that the websites have no obvious linear narrative or "next page" or conclusion (users move in a maze of text and navigation choices, some leading far away); lack a popular genre name (like infomercial), meaning that users come to them without a clear idea of how to perceive them; have an unpredictable mix of information and promotion, content, verbal style, visuals, and layout; and often present safety and risk information in small font, in cumbersome un-bulleted blocks of text, detached from promotional text and videos, and below a page's scrolling "fold." Source: EurekAlert! 6/30/10 

New Lung Cancer Drug Shows Dramatic Results for Shrinking Tumors

Patients with a specific kind of lung cancer may benefit from a Phase III clinical trial offered by the Moores University of California San Diego (UCSD) Cancer Center. The new drug, crizotinib, under development by Pfizer, showed dramatic results in reducing lung cancer tumors in some patients during Phase I and II clinical trials. "The results of the first two trials have been very encouraging," said Lyudmila Bazhenova, MD, assistant clinical professor at UC San Diego School of Medicine and a member of the Moores UCSD Cancer Center. "The Phase III clinical trials will be critical in determining if this drug goes to market." According to a preliminary study presented at the 2010 meeting of the American Society of Clinical Oncology, Phase I/II clinical trials demonstrated that 57 percent of patients had their tumors reduced and at eight weeks of the treatment, 87 percent showed disease stabilization. In some patients with non-small cell lung cancer (NSCLC), the anaplastic lymphoma kinase (ALK) gene may move and fuse with another gene, EML4. The resultant fusion produces an enzyme that promotes lung cancer cell growth. This fusion happens in approximately four percent of NSCLC patients. The chances of a patient having the fusion gene increases if they have the adenocarcinoma subtype of lung cancer, or are nonsmokers or former light smokers, among other characteristics. Those patients have an approximate 20 percent chance of having this mutation. Crizotinib inhibits the enzyme, allowing the cancer cells to die off. The Phase III clinical trial will compare crizotinib with standard-of-care chemotherapy in the treatment of ALK-positive recurrent NSCLC. Through a randomized selection process, patients will either be treated with chemotherapy or crizotinib. If the patients who are given the chemotherapy do not respond to treatment, they will be given crizotinib at the end of the trial. Source: EurekAlert! 6/22/10 

Department of Defense Helps Move Spinal Cord Injury Treatment Closer to Clinical Trials

The United States Department of Defense Spinal Cord Injury Research Program has announced a grant of more than $1 million to support research at the Robarts Research Institute at The University of Western Ontario (Western). The spinal cord injury research team of Gregory Dekaban, Arthur Brown, Lynne Weaver and Paula Foster, in collaboration with Brian Kwon of the University of British Columbia and Kyle Petersen of the U.S. Naval Medical Research Center, is working on a new therapy designed to limit the damage caused by inflammation immediately following spinal cord injury. The grant will move their work, led by Dekaban, closer to a clinical trial. Spinal cord injury occurs in two stages. The first is the physical injury from trauma; the second stage, that extends the initial damage, is caused in large part by inflammation in the spinal cord. "This antibody therapy is designed to be given by intravenous injection as soon as possible after a person comes into the emergency department with a spinal cord injury, or at least within 24 hours," explains Dekaban, a Robarts Scientist in the Molecular Brain Research Group and Professor in the Department of Microbiology and Immunology at Western's Schulich School of Medicine & Dentistry. "In our preclinical models, it's been shown to make a significant improvement in recovery. This antibody treatment could also be effective for traumatic brain injury." The antibody targets a protein known as CD11d on the surface of inflammatory cells that circulate in blood. CD11d is required by white blood cells to leave the bloodstream and enter the injured spinal cord. The anti-CD11d antibody is designed to block that process. By blocking the entry and retention of these white blood cells at the site of injury, the researchers successfully reduced inflammation and improved neurological recovery in preclinical models of spinal cord injury. The research at Robarts so far has employed a mouse antibody that recognizes human CD11d. This new award from the Spinal Cord Injury Research Program funded by the Department of Defense Congressionally Directed Medical Research Program will support the development of a humanized antibody suitable for use in a clinical trial. This research will be carried out in conjunction with Eli Lilly and Company. Source: EurekAlert! 6/21/10 

Study Examines Biomarkers for Malignant Gliomas

The Brain Tumor Unit at the Moores University of California, San Diego (UCSD) Cancer Center in La Jolla is launching a clinical trial that will examine the use of biomarkers to advance the treatment of malignant gliomas, brain tumors that start in the brain or spinal cord tissue. The Brain Tumor Unit comprises physicians and researchers from neurosciences, neurosurgery, neuropathology, neuroimaging, radiation oncology, and neuropsychology in one team—engaging everyone to advance the patient’s care, according to Bob Carter, MD, PhD, chief of the division of neurosurgery at UC San Diego Medical Center and the Moores UCSD Cancer Center. The group is focused on conducting research using personalized medicine (for example, use of biomarkers) and clinical trials to improve the treatment of brain tumors. One study involves the molecular target platelet-derived growth factor receptor (PDGFR). It is involved in cell signaling, and is over-expressed in 15 percent of primary gliomas and 60 percent of secondary gliomas. The study will identify those patients with an over-expression of PDGFR, in order to identify those patients most likely to respond to a drug called Nilotinib. The Phase II study will be led by Santosh Kesari, MD, PhD, chief of the division of neuro-oncology in the UCSD Department of Neurosciences and director of neuro-oncology at the cancer center. “We intend to accelerate personalized therapies for each patient based on an in-depth understanding of each patient’s individual tumor,” said Kesari. “By looking at the underlying genetics of the tumor combined with clinical data, we hope to optimally tailor treatment and doses.” He added that if the study results are positive, it will underscore the need for more biomarker-based studies and open up novel approaches to treat cancer. Source: Newswise 6/15/10 

Topical Treatments Provide Effective Local Pain Relief

Gels, creams, and sprays containing painkillers such as ibuprofen, diclofenac, ketoprofen, and piroxicam are safe and effective treatments for local pain, according to Cochrane Researchers. A new systematic review they have conducted shows that topical nonsteroidal anti-inflammatory drugs (NSAIDs) are more effective than placebos for treating short-term pain and have few side effects. Topical NSAIDs are usually applied as gels, creams, or sprays to the specific areas of the body where pain is felt. In many countries, they are routinely prescribed for local pain relief of mild to moderate pain. Topical NSAIDs are considered to pose less risk of adverse effects than oral drugs of the same type because they are rubbed into the skin and therefore do not reach high concentrations in the blood. The researchers analyzed data from 3,455 participants in 31 studies. Participants were given either topical NSAIDs or placebos, typically to treat short-term pain caused by sprains, strains, or sports injuries. Most of those taking part were treated for between one week and a fortnight. NSAIDs were successful at reducing pain by 50 percent or more in more than six out of 10 cases, compared to four out of 10 for placebos. Topical diclofenac, ibuprofen, ketoprofen, and piroxicam seemed to provide the best results, but it was not possible to distinguish between them with certainty. Source: EurekAlert! 6/15/10 

Software Aids Tracking of Potential Conflicts of Interest

Thousands of faculty and students conduct research of varying types across Penn State's 24 campuses. They also are involved in many other projects and activities both through their positions with the university and elsewhere in the community. Because of this, it's not uncommon for potential conflicts of interest to arise. "Most conflicts can be managed and do not automatically disqualify a transaction or relationship from occurring," said Candice Yekel, the person responsible for overseeing potential conflicts of interest for the university. "The important thing is that the university is made aware of all potential conflicts of interest, so that such transactions are transparent and appear appropriate to external parties." In June, Penn State made it easier to self-report potential conflicts of interest for more efficient and effective tracking with the roll-out of a new electronic system known as COINS (Conflict Of INterest System). According to Harold L. Paz, chief executive officer of Penn State Milton S. Hershey Medical Center, senior vice president for health affairs at Penn State, and dean and of the College of Medicine, this is a critical time in which to focus on compliance in this area. "We're seeing greater scrutiny from Congress, our federal sponsors and the public with respect to the perception of conflict between research missions and outside interests of the researcher. Because of this scrutiny, we have in place an annual disclosure process in the College of Medicine to be proactive in identifying and mitigating any potential conflicts of interest associated with our research." COINS is web-based, making it simple for any researcher to submit a disclosure. The system also automates the administrative processes involved in reviewing and processing more than 1,000 disclosures. In addition, the activities associated with the conflict of interest committees and the maintenance of management plans all are handled electronically. "We simply could not handle the volume of disclosures now or in the future without an electronic system," said Yekel. Source: Penn State Live 6/10/10 

University Opens New Respiratory Research Clinic

Olympic swimmer and television personality Sharron Davies was in Nottingham, United Kingdom, in June to open a new clinical trials unit that will take treatments for respiratory illnesses such as asthma from laboratory bench to bedside. The Nottingham Respiratory BRU Clinical Trials Unit will bridge the gap between treatment and research by offering clinical services to National Health Service (NHS) patients with respiratory disease, while recruiting volunteers for studies into developing new drugs and therapies to help people to manage their illness. The new center is part of the Nottingham Respiratory Biomedical Research Unit (NRBRU), a partnership between the University of Nottingham and Nottingham University Hospitals NHS Trust. Funded with £6.1 million by the Department of Health's National Institute for Health Research, it is one of 16 Biomedical Research Units in the U.K. focusing on "translational research"—taking advances and innovations in basic medical research out of the laboratory and into NHS practice, with the ultimate aim of improving patient care. Davies unveiled the new unit, based at the Nottingham City Hospital campus, on June 9. She said: "I am delighted to have been invited to open the new Nottingham Respiratory BRU Clinical Trials Unit. Asthma is a serious disease and a health issue that many competitive swimmers have to overcome to achieve success in their sport. It is exciting to think that the clinical trials that will be conducted in Nottingham could one day make a real difference to the millions of people worldwide who suffer from this debilitating illness." Among the research being carried out at the NRBRU that will benefit from the new clinical trials unit is a study looking at whether a tablet originally produced for people with diabetes could be used to treat mild asthma. "We have found that although, it may not benefit their own health in the short term, patients are often keen to take part in clinical trials because they like the idea that their involvement could in the future give relief to others who suffer from the same debilitating conditions," the study's leader said. Source: EurekAlert! 6/10/10 

Late-Stage Ovarian Cancer Treatment Shows Promise in Two-Drug Phase I Trial

The combination of decitabine and carboplatin appears to improve the outcome of women who have late-stage ovarian cancer. In an upcoming issue of the journal Cancer, Indiana University researchers report four of 10 patients who participated in a Phase I clinical trial had no disease progression after six months of treatment. One patient experienced complete resolution of tumor tissue for a period of time. Women participating in the study were between 51 and 71, and had previously exhausted all approved treatments for ovarian cancer. They enrolled in an Indiana University Melvin and Bren Simon Cancer Center clinical trial designed to increase their sensitivity to the commonly prescribed ovarian cancer drug, platinum-based carboplatin. Carboplatin is the most efficient drug therapy for ovarian cancer, but patients with recurrent disease become resistant to the drug after one or two rounds. Decitabine was first used to treat the study patients intravenously daily for five days, followed on the eighth day with carboplatin. After a month, the regimen begins again. Six months after the trial began, four of the patients had no disease progression. At eight-and-a-half months, seven patients were alive (and at press time, still alive). Cancerous tissue in one of the patients shrank completely. Encouraged by the results of the trial, which determined the safety of two different dosing regimens, a Phase II trial is now under way with 17 patients already enrolled. Why trial patients were responsive to the combination of decitabine and carboplatin is not yet known, but based on the literature and an analysis of biopsy tissue and blood samples, researchers suspect decitabine reactivates tumor suppression genes that are turned off in ovarian cancer cells. Source: EurekAlert! 6/9/10 

New Comparative Effectiveness Program to Focus on Cardiothoracic and Orthopedic Studies

A leading authority in comparative effectiveness research (CER), Dr. Art Sedrakyan, has been appointed director of a new collaborative program in CER based in the Department of Public Health at Weill Cornell Medical College in New York. The program's research portfolio will initially focus on devices, drugs, and alternative approaches for the management of orthopedic conditions and cardiovascular diseases, with the intent of using this to build a comprehensive program in CER for the entire medical center. As a result of the 2009 American Recovery and Reinvestment Act, $1.1 billion of new federal funding has been designated for CER, which involves studies aimed at identifying which treatments provide the greatest benefit to different patient groups, ultimately to improve care for all patients. Sedrakyan previously served as a medical officer and commissioner's fellow at the Food and Drug Administration Center for Devices and Radiological Health, and as senior service officer and senior adviser at the Agency for Healthcare Research and Quality Center for Outcomes and Evidence. Source: Newswise 6/9/10 

FDA Approves First Human Neural Stem Cell Trial to Treat Brain Tumors

City of Hope researchers in California in June received approval from the U.S. Food and Drug Administration (FDA) to conduct the first-in-human study of a neural stem cell-based therapy targeting recurrent high-grade gliomas, the most aggressive type of brain tumor. Karen S. Aboody, MD, associate professor in City of Hope's Department of Neurosciences, leads the research team that developed this treatment strategy. Jana Portnow, MD, assistant professor and assistant director of the Brain Tumor Program at City of Hope, is the principal investigator for the clinical trial. Aboody and her colleagues were the first to demonstrate in 2000 the inherent propensity of neural stem cells to home in on invasive tumor cells, also known as tropism, even migrating from the opposite side of the brain or across the blood-brain barrier. Aboody's research team has since harnessed the tumor-tropism of neural stem cells to deliver therapeutic agents to invasive tumor sites, which they demonstrated in laboratory testing. The therapy uses a genetically modified human neural stem cell line to deliver a prodrug-activating enzyme (cytosine deaminase) to brain tumor sites. This enzyme converts a relatively nontoxic prodrug (5-Fluorocytosine, 5-FC), which is delivered systemically, into an active cancer-fighting chemotherapeutic (5-Fluorouracil, 5-FU). In effect, this stem cell-mediated strategy achieves production of the chemotherapeutic drug only in the area of the tumor. This investigational treatment concentrates anticancer compounds at tumor sites while minimizing exposure of surrounding healthy tissue. The clinical trial will begin accepting patients this summer, with the goal of enrolling 12 to 20 patients with recurrent high-grade gliomas. The modified neural stem cells will be injected during surgery into the wall of the cavity remaining after tumor tissue has been removed. Study patients then receive daily doses of the prodrug 5-FC for one week. Based on Aboody's laboratory findings, once the 5-FC crosses the blood-brain barrier, the neural stem cells will convert the 5-FC to the active chemotherapy agent, 5-FU, at tumor sites in the brain. The Phase I safety trial will assess the maximum tolerated dose of the therapy, and is supported by a grant from the National Cancer Institute, part of the National Institutes of Health. Source: EurekAlert! 6/8/10 

Partnership to Advance Use of Molecular Imaging in Clinical Trials

Cardinal Health and the University of Washington have announced a public-private collaboration designed to advance the use of molecular imaging in clinical investigations and trials. Through this collaboration, the university's Department of Radiology will relocate a portion of its on-campus molecular tracer laboratories into Cardinal Health's PET manufacturing facility located in downtown Seattle. The department will have access to Cardinal Health's cyclotron, radiopharmaceutical products, and research support services to aid in the efficient operation of its research facility. Source: PRNewswire 6/4/10

Oncologists Fight Leukemia with Two-Pronged Therapy

A new therapy mounts a double-barreled attack on leukemia, targeting not just the cancer cells but also the environment in which those cells live and grow, University of Florida researchers report. Like striking an enemy camp directly as well as cutting off its source of food and other resources, the agent, called Oxi4503, poisons leukemia cells and destroys the blood vessels that supply them with oxygen and nutrients. Use of the treatment in mouse models of acute myelogenous leukemia is described online and in an upcoming print issue of the journal Blood. The researchers plan human tests of the drug later this year. The U.S. Food and Drug Administration quickly gave its approval in April for a Phase I clinical trial. The initial two-year trial is not designed to determine whether the drug works, but rather to determine the maximum tolerable dose. It will involve three dozen individuals age 18 and older whose cancer is growing despite previous treatment. Source: EurekAlert! 6/3/10

New Gene Therapy Proves Effective in Treating Severe Heart Failure

Researchers at Mount Sinai School of Medicine have developed a new gene therapy that is safe and effective in reversing advanced heart failure. SERCA2a (produced as Mydicar®) is a gene therapy designed to stimulate production of an enzyme that enables the failing heart to pump more effectively. In a Phase II study, SERCA2a injection through a routine minimally invasive cardiac catheterization was safe and showed clinical benefit in treating this patient population and decreasing the severity of heart failure. The data were presented at the recent Heart Failure Congress of the European Society of Cardiology in Berlin. The CUPID (Calcium Up-regulation by Percutaneous administration of gene therapy In cardiac Disease) trial is a randomized, double-blind, placebo-controlled study, which enrolled 39 patients with advanced heart failure to study the safety and efficacy of SERCA2a. Patients were randomized to receive SERCA2a gene delivery in one of three doses or placebo and were evaluated over six months. The treatment is delivered directly to the patient's heart during a routine outpatient catheterization procedure. The CUPID Trial is funded by Celladon Corp., makers of Mydicar. Source: EurekAlert! 6/3/10

Investigators Perform Head-to-Head Comparison of Incontinence Treatments

As part of a national clinical trial, University of Texas (UT) Southwestern Medical Center researchers found little difference in effectiveness between two popular treatments for one of the most common ailments among American women: stress urinary incontinence. UT Southwestern surgeons and colleagues at eight other sites compared the outcomes of two surgical procedures designed to alleviate symptoms of stress urinary incontinence. The study, available online in the New England Journal of Medicine, shows that both surgical procedures--transvaginal sling (TVT) and transobturator midurethral sling (TOT)--appear to be similarly effective in women up to 12 months after the procedures were performed. The TVT sling, introduced in 1996, involves placing a thin strip of polypropylene mesh weave transvaginally and behind the urethra and pubic bone. The strip acts as a kind of scaffolding that supports the urethra, diminishing urine leakage. The more recently developed TOT sling reduces the risk of bladder or bowel injury by passing the sling laterally into the groin through two small incisions in the upper thigh. This method works in the same way as the TVT, by supporting the urethra. Controversy exists as to which sling is more effective and which might be associated with a greater risk of complications. Funding for this study was provided by the National Institute of Diabetes and Digestive and Kidney Diseases and by the National Institute of Child Health and Human Development. Source: EurekAlert! 6/2/10

Trial Finds Azithromycin Pills Equal to Penicillin Shots for Treating Early Syphilis

In a clinical trial involving HIV-negative volunteers with early-stage syphilis, researchers have found that antibiotic pills (azithromycin) are as effective as penicillin injections in curing early-stage syphilis. The study was supported by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. Edward W. Hook III, MD, of the University of Alabama at Birmingham, led the trial. Between June 2000 and March 2007, HIV-negative volunteers aged 18 to 55 enrolled at eight sites in the United States and Madagascar. Volunteers were randomly assigned to receive either two injections of benzathine penicillin G or four tablets of the broad-spectrum antimicrobial macrolide drug azithromycin. Of 517 total enrollees, 469 were included in an intention-to-treat analysis. Among azithromycin recipients, 77.6 percent (180 out of 232) were cured of syphilis, while cure rate among penicillin recipients was 78.5 percent (186 out of 237). Although long-acting penicillin delivered by injection is recommended as the preferred treatment for early syphilis, the authors note that this therapy has shortcomings, particularly in resource-limited settings. Penicillin injections can cause allergic reactions, and the drug must be refrigerated and administrated by trained personnel. The orally administered azithromycin may provide a good alternative for treating HIV-negative people with early-stage syphilis, the scientists conclude. They note that there is a potential for syphilis-causing bacteria to acquire resistance to macrolide drugs such as azithromycin, and they recommend continued research into this possibility. Source: EurekAlert! 6/1/10

"Orphan Drug" Research Offers Hope

In addition to their suffering, rare disease patients often have to face the harsh reality that few pharmaceutical companies will ever be able to offer new treatments for their condition because the costs of new treatments will never be recovered from such a small market, but there are ways they can be helped. The U.S. Food and Drug Administration's (FDA's) "Orphan Drug Designation" offers a wide range of benefits that help organizations developing treatments for diseases and conditions affecting fewer than 200,000 patients in the United States. It was recently granted to McGill University for research conducted at the university's health center into the use of the drug fenretinide for the treatment of pulmonary infections caused by Pseudomonas aeruginosa in patients with Cystic Fibrosis (CF). "We strongly believe that fenretinide has the potential to improve morbidity and prognosis in CF patients at different levels," said Dr. Danuta Radzioch, a professor of experimental medicine at the center and McGill's Faculty of Medicine. "Our research has demonstrated that fenretinide reduced lung inflammation as well as the frequency and the severity of pulmonary infections." Fenretinide is a drug that was originally investigated for potential use in the treatment of cancer but has not been commercially available. Orphan Drug Designation provides opportunities for grant funding toward clinical trial costs, tax advantages, FDA user-fee benefits, and seven years of market exclusivity in the U.S. following drug approval by the FDA. "We felt extremely proud when McGill received the FDA's Orphan Drug status for fenretinide. This is a very important step in our development and commercialization objectives for this truly innovative approach for the management of pulmonary infections in CF patients" said Dr. Mounia Azzi, Investment Manager at MSBi Valorisation, a partner organization. The next step will be a clinical trial to assess safety, tolerability and efficacy of fenretinide in CF patients, to be undertaken in collaboration with the Montreal Chest Institute. Source: EurekAlert! 6/1/10

Researchers Play Major Role in New Center on Electronic Health Information Privacy

Slowly, but steadily, the U.S. healthcare community is moving into the digital age by shifting medical records from paper to electronic information systems. This movement raises serious concerns about security and privacy of patients' medical information. In an attempt to put these concerns to rest, the U.S. Department of Health and Human Services has awarded $15 million to create a new center for health information and privacy. The center, which will be headquartered at the University of Illinois, will include researchers from Vanderbilt University; University of California, Berkeley; Carnegie Mellon University; Dartmouth College; Harvard Medical School; Johns Hopkins University; Northwestern Memorial Hospital; Stanford University; University of Massachusetts, Amherst; and the University of Washington. It is one of four healthcare research centers established and funded for four years with American Recovery and Reinvestment Act of 2009 funds as part of the $60 million Strategic Healthcare Information Technology Advanced Research Projects on Security program. Source: EurekAlert! 5/28/10

Institute Launches New Melanoma Research Center

In an effort to meet the rising rates of melanoma head-on, the Wistar Institute in May announced the creation of the Wistar Institute Melanoma Research Center. The center brings together scientists, physicians, the life sciences industry, and melanoma advocates in saving lives by advancing new and better therapies for this deadly disease. In addition to providing a base for new melanoma science, the center represents the hub of activity that connects scientists and physicians at universities, independent research institutions, medical centers, and pharmaceutical companies, across the nation and the world. Their combined efforts, driven and supported by the melanoma advocacy community, will bring about new drug trials and renewed hope for melanoma patients and their families, an institute spokesperson says. Source: Newswise 5/27/10

National Trial Shows Carotid Artery Surgery and Stenting Equally Effective in Preventing Stroke

Physicians now have two safe and effective options to treat their patients at risk for stroke, says a researcher at Mayo Clinic who led a large, National Institutes of Health (NIH)-funded, national clinical trial testing surgery or use of a stent to open a blocked carotid artery. The results, published in the May 26 online issue of the New England Journal of Medicine, also show "excellent safety and long-term results for patients with warning signs for stroke as well as for patients without such warning signs," says the national principal investigator, Thomas G. Brott, MD, professor of neurology and director for research at the Mayo Clinic campus in Florida. Compared to other large international stroke prevention trials, Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) is unique in that approximately half of enrolled patients did not have symptoms of carotid disease, while the other half had experienced recent symptoms such as a minor nondisabling stroke or transient ischemic attack. The CREST results can inform treatment decisions for both groups of patients, in contrast to results from recent trials completed in Europe. This is important, because more than half of the approximately 140,000 carotid surgeries and stent procedures performed in the U.S. each year are performed for patients without symptoms. Researchers say that while the findings show surgery and stenting had very good long-term outcomes, they differed in the weeks following the procedure—patients who received a stent had fewer heart attacks, and those treated surgically had fewer strokes. Age also made a difference, they say—people younger than 70 did slightly better with stents, while those over 70 had better results with surgery. The study was primarily funded by the National Institute of Neurological Disorders and Stroke and the National Institutes of Health, with support from Abbott Vascular Solutions, Inc. Source: EurekAlert! 5/26/10

Study Identifies Promising Treatment for Aggressive Lymphoma

New research illustrates that some patients with transformed lymphoma showed "remarkable" response to lenalidomide, an oral drug with few side effects. The international study, involving 24 medical centers in the United States and Europe, was presented at the American Society of Clinical Oncology annual meeting in June in Chicago. Forty-five percent of patients with transformed lymphoma treated with lenalidomide responded positively to this immunomodulatory medication, which kills lymphoma cells by activating the body's natural killer cells and by interrupting cancer cell signaling that leads to cell death. Of those patients, 21 percent showed complete remission, some for more than a year. Craig Reeder, MD, a Mayo Clinic hematologist, was principal investigator for the Phase II study at Mayo Clinic's Arizona campus. The study included 217 patients with aggressive lymphoma. Of those, 33 had transformed lymphoma and were treated with lenalidomide. These patients ranged in age from 42 to 84. More than half had stage IV disease, where the lymphoma has spread to multiple sites or organs. All patients had been treated with chemotherapy and some with stem cell transplant to curtail the cancer. The median number of previous treatments was four and ranged up to 12. Patients took lenalidomide pills (25 mg) daily for 21 days. For seven days, no medication was given. The medication continued until signs of cancer progression. Overall, 45 percent of patients responded positively to the therapy, but results varied by the particular type of transformed lymphoma. For transformed follicular lymphoma, the most common form of the illness, 13 of the 23 patients (57 percent) in this subgroup responded positively to lenalidomide. Ten patients with other types of transformed lymphoma did not respond. They included transformed chronic lymphocytic leukemia, small lymphocytic lymphoma, and others. Source: EurekAlert! 5/26/10

Vaccine Hope for Skin Cancer Sufferers

Univesity of Nottingham scientists have been given the green light to test a vaccine which they hope could reverse, and even cure malignant melanoma, the most deadly type of skin cancer. Scancell Holdings plc, led by Professor Lindy Durrant of the university's Division of Clinical Oncology within the School of Molecular Medical Sciences, believes the new vaccine, which targets tumour cells without damaging healthy tissue, could be successful in treating patients with malignant melanoma. "It is still at a very early stage and impossible to predict the outcome of the clinical trial, but if our results from the lab are replicated in patients, I think we have a good chance of dramatically improving the chances of successful treatment—we are hoping that the vaccine will cure between 10 and 20 percent of patients with malignant melanoma," Durrant said. Testing for the new SCIB1 vaccine has been given approval by the Gene Therapy Advisory Committee and the Medicines and Healthcare products Regulatory Agency and clinical trials are due to start shortly at Nottingham City Hospital and centers in Manchester and Newcastle. It will initially be given to patients who are suffering from advanced malignant melanoma which has spread to other parts of the body. The new vaccine works by activating the body's own natural defence systems—it contains DNA and genetic material from tumors, meaning it "switches" on the specific immune cells that target melanoma. This means that it targets only the cancer, and not the surrounding healthy tissue. Source: EurekAlert! 5/26/10

University Receives $12 Million for Regenerative Medicine Treatment Trials

A two-year, $12 million contract with the U.S. Department of Defense Office of Technology Transition (OTT) will jumpstart human trials of three innovative research programs that aim to replace scars and defects with healthy, functional tissues, announced officials of the University of Pittsburgh and the McGowan Institute for Regenerative Medicine in May at the Institute's Second Annual Open Session. The OTT mission emphasizes the rapid translation of preclinical research into human studies to bring successful therapies more quickly to everyday practice, said Alan Russell, PhD, director of the McGowan Institute, a joint effort of the university and the University of Pittsburgh Medical Center, and leader of the new program. "This initiative provides fiscal support and also represents a shared commitment to the goal of helping soldiers return to the lives they have put on the line for us," he said. "All these projects could deliver much-needed solutions for the ills that plague our wounded warriors. They are designed to give back what has been lost or taken away: normal tissues that function properly, adapting to our changing biological environment to keep us healthy and whole." The projects, if successful, could ultimately lead to interventions that also benefit civilians, noted Arthur S. Levine, MD, senior vice chancellor for the health sciences and dean, School of Medicine, University of Pittsburgh. "Muscle loss, bone damage, and severe scarring that restricts natural movement are not uncommon consequences of traumatic accidents or surgeries that require a large amount of tissue removal," he said. "We must find more ways to help individuals who are struggling with the aftermath of these potentially devastating problems." Source: EurekAlert! 5/25/10

Researchers Testing Vaccine to Help People Quit Smoking

In a unique twist to a decades-old health crisis, Michigan State University (MSU) researchers are testing a new vaccine to help people quit smoking and avoid relapses. Using a vaccine--as opposed to patches or gums, which attempt to wean people off nicotine--is a novel approach to the addiction that results in more than $192 billion in healthcare costs each year, according to federal estimates. The vaccine, called NicVAX, is being developed and manufactured by Nabi Biopharmaceuticals of Rockville, Md. It will be tested at 25 sites nationwide. Jonathan Henry, an associate professor with MSU's Department of Psychiatry and the Clinical and Translational Sciences Institute, is leading the clinical trial at MSU. "Using a vaccine to treat nicotine dependence is one of the most unique approaches to battling addiction," Henry said. "We are very hopeful this strategy will help smokers kick the habit." The vaccine works by preventing a smoker from "feeling good" while smoking. When nicotine enters the bloodstream, it quickly crosses the blood-brain barrier, triggering the release of stimulants such as dopamine that provide the smoker with a positive sensation, eventually leading to addiction. NicVAX stimulates the immune system to produce antibodies that bind with and prevent nicotine from crossing the blood-brain barrier, essentially preventing the highly addictive pleasure sensation experienced by smokers. Vaccine developers hope that prevention helps people quit smoking, and because the antibodies remain in the bloodstream for several months, the vaccine could be effective in preventing relapse. With current smoking-cessation therapies, relapse rates can be as high as 90 percent in the first year after a smoker quits. During the clinical trial, participants will receive the vaccine several times throughout a 12-month period. Results from the placebo-controlled study are expected to be available in early 2012. If the clinical trial proves successful, Nabi Biopharmaceuticals will seek Food and Drug Administration approval shortly thereafter. MSU will focus on about 50 of the study's hoped-for 1,000 nationwide participants. Source: EurekAlert! 5/21/10 

Drug in New Class of Targeted Therapies Shows Early Promise Against Blood-Related Cancers

A Phase I clinical trial of SNS-032, one of the first in a new class of drugs that inhibit cyclin-dependent kinases, demonstrated the drug's safety and potential clinical action against advanced chronic lymphocytic leukemia (CLL). Cyclin-dependent kinases are enzymatic proteins that are integrally involved in cellular metabolism, renewal, and signaling, and are thought to play key roles in the growth of cancers. The drug did not demonstrate any clinical effect against advanced multiple myeloma, although researchers hope it might still prove to have some benefit against this blood cancer as part of combination therapy. The paper is published online in the Journal of Clinical Oncology. "No drugs that target this cancer mechanism are on the market today," says study author David S. Siegel, MD, PhD, co-chief for multiple myeloma at the John Theurer Cancer Center of Hackensack University Medical Center in New Jersey. "I am hopeful that larger studies will show that this targeted therapy is useful against a number of advanced B cell malignancies." Siegel and colleagues tested the new medication on 37 patients, including 19 with CLL and 18 with myeloma. Patients recruited to the study had advanced disease that was in relapse, and all had been through previous treatments with other medications. All patients were given SNS-032, and all were aware of what they were taking. To test both the drug's safety and the best potential dose, SNS-032 was given intravenously as a "loading" dose--an initially higher dose that is then reduced to a maintenance level--over five minutes. This was followed by a six-hour infusion given to all patients on a weekly basis for three consecutive weeks. Although the primary purpose of the study was to test the maximum safe dose that could be given to patients, the researchers also looked at whether the medication had an effect on disease processes. One patient with CLL had more than a 50 percent reduction in measurable disease, but no improvement in disease markers in the blood. Another CLL patient had stable disease for four courses of treatment. For multiple myeloma, two patients had stable disease with treatment and one had normalization of spleen size, which is an indication of a reduction in blood cancer activity. Looking at blood test results for the patients, the researchers found anticancer activity. The drug appeared to inhibit cyclin–dependent kinases 7 and 9, two of the three enzymatic proteins targeted in this study. They also caused apoptosis, or cell death, in cancer cells. Researchers from the University of Texas M.D. Anderson Cancer Center, Emory University, University of Maryland, City of Hope, Stanford University, and Sunesis Pharmaceuticals also contributed to this study. Source: EurekAlert! 5/19/10

One-a-Day Heart Polypill to be Tested in New International Trial

Researchers will explore whether a new, very low cost, one-a-day combined "polypill" could reduce the risk of heart attacks, strokes, and other cardiovascular problems across the world in a major new international trial that launched in May. The new "Red Heart Pill" contains low-dose aspirin, a statin, and two blood pressure-lowering medicines in a single polypill. It is expected to be substantially cheaper than existing medications to combat cardiovascular problems. Researchers are now recruiting 2,000 volunteers who are at high risk of heart attack or stroke, or who have already had such a cardiovascular event, for a two-year trial of the Red Heart Pill. The trial--called UMPIRE (Use of a Multidrug Pill In Reducing cardiovascular Events)--launched at the Imperial College London in the U.K. and at other centers in Ireland, the Netherlands, and (pending regulatory approval) in India. Related trials began earlier in the year in New Zealand and Australia, and plans for further trials are also under way in Brazil, Canada, China, and South Africa. Collectively, these parallel trials will include around 7,000 participants in 10 countries. The researchers behind the trial will investigate whether patients are more likely to stick with a preventive treatment regime using a single, one-a-day polypill, rather than multiple tablets. The researchers will also explore whether the Red Heart Pill is effective at reducing blood pressure and lowering cholesterol. If the treatment strategy is effective, the researchers plan to establish how the polypill could be made available to people on low incomes in countries like India, where 80 percent of healthcare is paid out of pocket and the majority of people do not currently have access to cardiovascular drugs. It is expected that the Red Heart Pill could be made available in low-income countries at a substantially lower cost than separate medications, providing a cost-effective approach that could potentially save millions of lives across the world. Source: EurekAlert! 5/17/10

Trials Begin on Potent New Hepatitis C Drug

The first clinical trials have started on a new investigational drug, discovered by researchers at Cardiff University, which is being developed to treat infections caused by hepatitis C virus, which can lead to liver cancer, cirrhosis, and death. The current treatment involves two drugs--ribavirin and interferon, which has to be given as an injection. Side effects are often severe and lead to patients failing to complete the treatment. The new drug, INX-189, is taken orally, and was first prepared at the Welsh School of Pharmacy in November 2008. Laboratory tests showed it killed 90 percent of the virus at very low (nanomolar) concentration, making it one of the most potent compounds of its kind developed to date. The U.S. pharmaceutical company Inhibitex, which owns the licence to INX-189 and has been working with the Cardiff team, has now started trials in healthy volunteers to assess the compound's safety. A second trial, which would evaluate the compound's effectiveness, may follow later this year. Prof. Chris McGuigan of the Welsh School of Pharmacy, academic lead on the project, said: "This is still a very early stage of the trials process. However, progress has been encouraging so far, going from the laboratory to human trials within 18 months. We believe that INX-189 offers the possibility of more potency against hepatitis, more rapid action in the liver, and fewer side effects than existing treatments." Cardiff University and Inhibitex filed a patent on INX-189 earlier this year. It has been cleared for human clinical trials by the Food and Drug Administration in the U.S. Source: EurekAlert! 5/14/10

Bone Marrow Stem Cells Show Promise for Multiple Sclerosis

A groundbreaking trial to test bone marrow stem cell therapy with a small group of patients with multiple sclerosis (MS) has been shown to have possible benefits for the treatment of the disease. Bone marrow stem cells have been shown in several experimental studies to have beneficial effects in disease models of MS. The research team, led by Neil Scolding, Burden Professor of Clinical Neurosciences for the University of Bristol and North Bristol NHS Trust in the United Kingdom, have now completed a small trial in patients with MS to begin translating these findings from the laboratory to the clinic. The Bristol team report on this pioneering trial in an article published online in Clinical Pharmacology and Therapeutics. Under general anesthesia, bone marrow was harvested from the patients. The marrow cells were filtered and prepared so that they could be injected into a patient's vein later the same day. The procedure was well tolerated and the participants were followed up for a year. No serious adverse effects were encountered. The results of clinical scores were consistent with stable disease. The results of neurophysiological tests raised the possibility of benefit. Prof. Scolding said: "We are encouraged by the results of this early study. The safety data are reassuring and the suggestion of benefit tantalizing. A larger study is required to assess the effectiveness of bone marrow cellular therapy in treating MS. We are hopeful that recruitment to this Phase II/III study may begin toward the end of this year." The study has been funded by the Adrian Wright Bequest, the Patrick Berthoud Charitable Trust, the Silverman Family Foundation, the Myelin Project, the Captain SK Trust, and the Burden Trust. Source: EurekAlert! 5/5/10

University Receives $10 Million Federal Grant to Transform Dental Research Clinics

The University of Illinois at Chicago (UIC) College of Dentistry has received a $10 million federal grant to transform its research facilities into a state-of-the-art clinical and translational research center. The grant, part of the American Reinvestment and Recovery Act obtained through the National Institutes of Health, will be used to construct a clinical research center, create core facilities, and refurbish the remaining 23,000 square feet of laboratory space that was not completed in an earlier construction phase, said Dr. Bruce Graham, dean of the UIC College of Dentistry. Once the construction is complete, the entire 39,000 square feet of laboratory space at the college will be upgraded, he said. "This is truly a tremendous boost for us," Graham said. "We have some young faculty members who have a great deal of potential, and this will give all of our researchers the best facilities in which to continue their outstanding work. It will also allow us to link our basic scientists to clinical research to create a spectrum for translational research." Among the many projects is a new clinical research center that will serve as a satellite facility for UIC's Center for Clinical and Translational Science. The center will be located on the first floor and will be managed by the new head of periodontics and director of clinical research, Dr. Thomas Hart. The new clinical research center will include studies of patient populations with caries, periodontal diseases, and oral pathologies, and the impact of nutrition and systemic diseases on oral health, including oral inflammation, implants, wound healing, and surgical outcomes. Source: Newswise 4/22/10 

Drug May Treat Cystic Fibrosis and Other Nonsense Mutations Diseases

Inherited diseases such as cystic fibrosis can be caused by genetic "nonsense mutations" that disrupt the way human cells make proteins. David Bedwell, PhD, a professor in the University of Alabama at Birmingham Department of Microbiology, says scientists are now closer to producing drugs that will fix this disruption and drastically improve treatment of genetic disease. Bedwell is a renowned researcher on the select group of genetic alterations called nonsense mutations--DNA alterations that can lead to nonfunctional or missing proteins. He presented recent findings on an experimental drug that may help to treat some cystic fibrosis patients during the Experimental Biology 2010 conference in Anaheim, Calif., April 26. This drug ataluren (formerly called PTC124) also holds promise in treating more than 2,400 different genetic disorders caused by nonsense mutations. Ataluren is now being tested in humans for its effectiveness in treating Duchenne/Becker muscular dystrophy, cystic fibrosis, hemophilia A, hemophilia B, and other conditions. The research is a partnership with Bedwell and the university's Gregory Fleming James Cystic Fibrosis Research Center. It is funded by PTC Therapeutics Inc. with assistance from the National Institutes of Health. Source: EurekAlert! 4/26/10 

Old Drug with a New Purpose May Offer Hope for Children

A new Phase I clinical trial sponsored by the Vermont Cancer Center at the University of Vermont and Fletcher Allen Health Care has opened to test the investigational drug DFMO, or alpha-difluoromethylornithine, as a treatment for the pediatric cancer neuroblastoma. According to researchers at the Cancer Research Center of the University of Hawaii and at the Vermont Cancer Center, the study will monitor the safety of DFMO usage among neuroblastoma patients and test whether the drug is effective in reducing or eradicating neuroblastoma tumor cells. DFMO is a proven therapy for Trypanosomiasis, or "African Sleeping Sickness." Discovered in the 1970s, the drug was approved by the Food and Drug Administration and demonstrated few side effects in patient usage. In recent years, it has attracted renewed interest from researchers as a possible treatment for certain cancers. One of the first to study DFMO in relation to neuroblastoma was André Bachmann, PhD, MS, and associate professor at the University of Hawaii's Cancer Research Center. Bachmann has teamed up with Giselle Sholler, MD, a pediatric oncologist and researcher at the Vermont Cancer at the University of Vermont and Vermont Children's Hospital at Fletcher Allen Health Care, and they have demonstrated evidence of the drug's ability to cure neuroblastoma cancers in mice by inhibiting an enzyme implicated in aggressive tumor development. Bachmann and Sholler have continued this research collaboration in moving the laboratory findings to an actual drug trial. Sholler is the principal investigator of the clinical study, and worked with Bachmann to coquthor the protocol, which uses DFMO alone and in combination with a second drug, etoposide. The trial has now opened in Vermont, with more sites within the Neuroblastoma and Medulloblastoma Translational Research Consortium expected, including Kapiolani Medical Center in Honolulu. The first patient in the trial was enrolled in March, and is currently under treatment. Source: EurekAlert! 4/14/10 

New Targeted Therapy Effective in Treating Advanced Prostate Cancer

An experimental drug is showing promise for the treatment of men with an aggressive form of advanced prostate cancer. A new multicenter study has concluded that the targeted therapy MDV3100 is safe and effective for patients with castration-resistant prostate cancer, known for its poor prognosis and limited treatment options. The research, led by investigators at Memorial Sloan-Kettering Cancer Center, appears early online and in an upcoming edition of The Lancet. According to the findings of the Phase I-II study, MDV3100 not only shrank patients' tumors, but also reduced serum levels of the tumor marker prostate-specific antigen (PSA), stabilized disease that had spread to soft tissues and the bone, and reduced the number of circulating tumor cells in the blood. "We were encouraged to see antitumor activity in men whose disease had spread to other parts of the body after either becoming resistant to previous hormone treatments or progressing following chemotherapy," said the study's lead author Howard Scher, MD, chief of the Genitourinary Oncology Service at Memorial Sloan-Kettering. "These findings strengthen the drug's potential to change the outlook for a group of patients who currently have limited effective treatment options from which to choose." In the current study, 140 patients were treated with doses of MDV3100 ranging from 30 to 600 mg daily. PET imaging, bones scans, and blood tests were used to assess the antitumor effects of the drug, which were observed at all dosages. Investigators reported declines in PSA of at least 50 percent in more than half of the patients and tumor regressions in 22 percent of the patients. Overall, two-thirds of patients had partial remissions or stable disease in tumors that had spread to soft tissue or bone. The findings also showed that the number of circulating tumor cells fell in 49 percent of patients, and 91 percent of patients who initiated therapy with favorable counts retained favorable counts during treatment. This is important because previous research shows that changes in circulating tumor cell counts after treatment were more predictive of survival than were changes in PSA, with favorable post-treatment counts associated with a 21-month median survival. Based on the positive results of the current study, a multinational, randomized Phase III clinical trial has begun to examine MDV3100 versus a placebo for the treatment of men with advanced prostate cancer who were previously treated with chemotherapy. The research was supported by Medivation; the Prostate Cancer Foundation, the National Cancer Institute, the Howard Hughes Medical Institute, and the Department of Defense Prostate Cancer Research Program Clinical Consortium (which includes Memorial Sloan-Kettering, the Oregon Health and Science University Knight Cancer Institute, the University of Washington, the Dana-Farber Cancer Institute, and M. D. Anderson Cancer Center). Source: EurekAlert! 4/14/10 

Statins May Slow Progression of Multiple Sclerosis

A study led by Univeristy of Calinfornia, San Francisco (UCSF) to examine the impact of statins on the progression of multiple sclerosis (MS) found a lower incidence of new brain lesions in patients taking the cholesterol-lowering drug in the early stages of the disease as compared to a placebo. Study participants received an 80 mg daily dose of atorvastatin, marketed by Pfizer Inc. as Lipitor. Although the study was small, with only 81 participants, and its primary endpoint, designed to evaluate MS progression in patients following their first attack, was not met, the researchers found over the 12-month course that 55.3 percent of participants did not develop new brain lesions when administered statins, compared to 27.6 percent of the placebo group. Study findings were presented April 14 by UCSF researchers during the annual American Academy of Neurology scientific meeting in Toronto. The trial was a Phase II, multicenter, randomized, placebocontrolled followup to a landmark study published by principal investigator Scott S. Zamvil, MD, PhD, associate professor of neurology at UCSF in Nature in 2002, after his laboratory first observed that statins cause T cell immune modulation that could be beneficial in MS and other autoimmune diseases. Co-led by Zamvil and Emmanuelle Waubant, MD, PhD, associate professor of neurology at the UCSF MS Center, the study tested whether the drug could be used to prevent conversion to definite MS in individuals who have had a first attack. "Our data [are] preliminary, and we need a larger study to confirm the effects of the drug and its magnitude. It is important that we understand how statins impact the progression of multiple sclerosis in order to better inform physicians and patients of their effect, since these drugs are so broadly used throughout the United States and the world, and to learn whether a relatively inexpensive oral therapy can slow the course of disease," said Waubant. The team employed MRI to look at the activity of the medication on the disease course. More than 150 patients were originally intended, but enrollment was stopped due to slow recruitment after 81 patients were randomized. In addition to UCSF, the trial involved Oregon Health & Science University, the Cleveland Clinic, Virginia Mason MS Center, Washington University School of Medicine John L. Trotter MS Center, Montreal Neurological Institute, Barrow Neurological Institute, University of Texas Southwestern Medical Center, University of Rochester, the Multiple Sclerosis Comprehensive Care Center at Univeristy of Southern California Keck School of Medicine, Yale MS Research Center, Jacobs Neurological Institute, Johns Hopkins University, and Mount Sinai School of Medicine. The research was performed as a project of the Immune Tolerance Network, a clinical research consortium headquartered at UCSF and sponsored by the National Institute of Allergy & Infectious Diseases. Atorvastatin, placebo, and additional support were provided by Pfizer. Biogen-Idec provided Avonex, an immune system regulator drug (interferon beta-1a) for study participants who displayed disease activity while on placebo or atorvastatin. Additional funding was provided by the Nancy Davis Foundation and the Maisin Foundation. Source: EurekAlert! 4/14/10 

Scientists Begin Phase II Trial for New Asthma Treatment

Scientists from the University of Southampton and Synairgen Research Ltd, a respiratory drug development company spun out from the university, have begun a Phase II study into the effectiveness of the drug interferon beta for asthma patients. An increase in the frequency of asthma attacks (also known as "exacerbations") is commonly triggered by cold or flu viruses, because the lungs of patients with the condition are unable to mount the strong immune response that normally protects healthy airways. When the infection spreads from the nose to the lungs, it also causes inflammation which leads to such exacerbations. A successful treatment to prevent virus-triggered asthma exacerbations would reduce the number of asthma patients suffering increased frequency of attacks, and subsequently potentially life-threatening deterioration of lung function, thereby greatly reducing emergency admissions to hospital. Professor Ratko Djukanovic, a clinical respiratory specialist at the university's School of Medicine and Southampton University Hospitals NHS Trust and director of the Southampton Respiratory Biomedical Research Unit, explains: "When common cold or flu viruses spread from the nose and throat to the chest of asthma patients, they can cause a rapid deterioration in their health. Our scientists in Southampton, led by the team of Professor Donna Davies, have found in laboratory-based tests that the lungs are able to protect themselves when the protein interferon beta is introduced. If the drug works as we hope it will, it could significantly improve the quality of life for these patients and lessen the number of patients admitted to hospital. However, it is important to stress that there are a number of stages before the drug could be made available to the public. We are particularly pleased to have been joined in this clinical trial by other lead asthma centres in the U.K. which have similar biomedical research units funded by the National Institute for Health Research." Over the next nine to 15 months, asthma patients taking part in the study who visit the Biomedical Research Unit at Southampton General Hospital will be given either interferon beta or a placebo by inhalation when they develop cold or flu symptoms. The results will be used to determine if inhaled interferon beta is a viable treatment for virus-triggered asthma symptoms. Scientists have already established that the drug was well tolerated in an earlier Phase I trial in asthma patients and that antiviral defences were activated. Richard Marsden, CEO of Synairgen, comments: "We are delighted to be starting this pivotal study. If these tests are successful, it could lead to a new treatment being on the market in four years or so. This is very important research, and showcases the best of British clinical science and interaction between industry and academic researchers." Once the study has begun in Southampton, it will be extended to other clinical trial sites around the U.K. Source: EurekAlert! 4/8/10 

Trial of Personalized Two-Drug Therapy for Brain Tumors Launched

Patients suffering from recently diagnosed malignant brain tumors called glioblastoma multiforme or a rare variant called gliosarcoma may be eligible to participate in a Phase II clinical trial at Cedars-Sinai Medical Center that combines two innovative drugs. Cedars-Sinai's Cochran Brain Tumor Center is the only site in California, and one of only 13 in the nation, offering this experimental therapy through the Brain Tumor Trials Collaborative (BTTC) based at M.D. Anderson Cancer Center in Houston, Texas. The two anticancer drugs, Avastin (bevacizumab) and Tarceva (erlotinib), work through different molecular mechanisms to attack brain tumors. Avastin inhibits vascular endothelial growth factor, a protein that contributes to the formation of blood vessels that tumors need for growth. Tarceva is designed to prevent tumor growth by blocking a signal pathway that controls cell division by binding to a cancer cell membrane receptor called epidermal growth factor. Although single-agent targeted therapies have not produced significant improvements in treating glioblastomas, laboratory experiments and studies in animals suggest that a combination approach may have greater impact. This two-drug combination is also in clinical trials for the treatment of other cancers, including non-small cell lung cancer and renal cell carcinoma. While all glioblastoma multiforme tumors share certain characteristics, they are not all genetically alike. This trial is specifically designed for those whose tumor cells have unmethylated MGMT promoter. This provides an especially strong study of the effects of the new two-drug approach, because these tumors are resistant to the type of chemotherapy typically prescribed for patients with glioblastoma. The two-drug therapy will be administered after standard treatment with temozolomide and radiation therapy. Because radiation has been found to increase activation of certain molecular factors that the two drugs target, it is theorized that radiation therapy may stimulate a greater antitumor effect from the drugs. The mission of the BTTC is to develop and perform hypothesis-based, state-of-the-art clinical trials in a collaborative and collegial environment, emphasizing innovation and meticulous attention to protocol compliance and data quality. The group is led by researchers at M.D. Anderson Cancer Center in Houston and includes investigators at Cedars-Sinai and 11 other cancer research and treatment centers across the nation. The other current members are Baylor University Medical Center, Dallas, Texas; Dana Farber Cancer Center, Boston, Mass.; M.D. Anderson Cancer Center in Orlando, Fla.; Medical University of South Carolina, Charleston; Memorial Sloan-Kettering Cancer Center, N.Y.; Methodist Hospital System, Houston, Texas; Northshore University Health System, Chicago, Ill.; Northwestern University Feinberg School of Medicine, Chicago, Ill.; Ohio State University A.G. James Cancer Hospital, Columbus; the University of Washington, Seattle; and the University of Texas Southwestern in Dallas. Source: Newswise 4/7/10

Clinical Trial to Test Whether Vaccine Can Effectively Treat Melanoma

Rush University Medical Center is leading a nationwide Phase III clinical trial to determine whether a promising vaccine for advanced melanoma can effectively treat the deadly skin cancer. An earlier Phase II trial of the experimental drug involving 50 patients with metastatic melanoma had stunning results; eight patients recovered completely and four partially responded to the vaccine. The vaccine being tested is called OncoVEX, initially developed to combat herpes virus. Researchers discovered accidentally that the vaccine attacked cancerous tissue when it was inadvertently placed in a Petri dish of tumor cells. The vaccine includes an oncolytic virus, a reprogrammed virus that has been converted into a cancer-fighting agent that attacks tumor cells while leaving healthy cells undamaged. OncoVEX also carries biological agents that boost the immune response to melanoma. The vaccine is injected directly into lesions that can be felt or seen, with or without ultrasound. The procedure is generally done in a physician's office. The earlier Phase II trial, an initial test of the vaccine's efficacy, included 50 patients with metastatic melanoma, or melanoma that had spread to other parts of the body, who had failed to respond to conventional treatment, including chemotherapy and immunological drugs such as interleukin-2. Response rates for those therapies are at best about 15 percent. By comparison, the overall response rate in the OncoVEX trial was 26 percent. Eight of the 50 patients were free of disease by the end of the trial period, which consisted of vaccination every two weeks, for a total of up to 24 injections or until disease disappeared. Four more patients were rendered disease-free after surgery or further vaccination of new lesions. Overall survival was 58 percent at one year, and 52 percent at two years. The results were reported last December in the Journal of Clinical Oncology. The vaccine worked not just on the cells that the researchers injected, but on lesions in other parts of the body that they could not reach. In other words, the vaccine prompted an immune response that was circulated through the bloodstream to distant sites. The new Phase III trial will enroll a total of 430 patients at centers across the U.S. As with the earlier trial, the vaccine will be injected directly into tumor nodules every two weeks for up to 24 treatments. Patients will be tracked for two years after the first dose is received. BioVex, in Woburn, Mass., which makes OncoVEX, is funding the study. Source: EurekAlert! 4/6/10

Drug Breakthrough in Fight Against Neglected Diseases

Scientists from the Drug Discovery Unit at the University of Dundee in Scotland--working with partners at the University of York and the Structural Genomics Consortium in Toronto--have made a major breakthrough in identifying new treatments for a fatal disease which infects tens of thousands of Africans each year. Their findings, published in Nature, describe a new approach to tackling the fatal parasitic disease human African trypanosomiasis (HAT), commonly known as sleeping sickness due to disturbance of the sleep cycle caused by parasites infecting the brain. The breakthrough made at Dundee shows promise for the development of effective, orally administered, low toxicity drugs to treat sleeping sickness. "This is one of the most significant findings made in recent years in terms of drug discovery and development for neglected diseases," said Professor Paul Wyatt, director of the Drug Discovery for Tropical Diseases programme at Dundee. "We now have a valid drug target for HAT and have found leads for drugs which can be dosed orally. These two findings represent significant strides in the development of a full blown drug against sleeping sickness suitable for clinical trials. HAT comes in two stages--we know the drug leads we have identified in this paper can treat the first stage, and we are very optimistic that we can now further develop them to treat the second, more serious stage." It is estimated that drugs may be ready for human clinical trials in around 18 months. The disease has two stages, the second of which is particularly difficult to treat in poverty-stricken rural areas, where many victims live. Of the two drugs currently available, one--an arsenic-based drug--has fatal side effects in around one in 20 patients, and the other, eflornithine, is costly, requires prolonged hospital treatment, and is not effective against all forms of the disease. Increasing reports of treatment failures with these drugs is causing concern that soon there may be no effective treatment for this fatal disease. In response to the need for new and safe treatments, the Dundee unit has already made good progress in developing compounds that have proved effective at killing the parasites, and that work well in the first stage of the disease. The compounds disrupt the enzyme N-myristoyl transferase, which is essential for survival and growth of the parasites. The Drug Discovery Unit at Dundee was formed in 2005 specifically to fill the void of research and development of drug targets for diseases of poverty like African sleeping sickness, leishmaniasis, and Chagas' disease, which afflict the developing world. Source: EurekAlert! 3/31/10

Developers of Welsh Shingles Drug Looking Toward Final Hurdle

A new Welsh-developed drug to help alleviate the suffering of shingles could move a step closer for patients if the final stage of testing is given the go-ahead. The drug (FV-100), discovered by Professor Chris McGuigan's team from Cardiff University's Welsh School of Pharmacy together with a virology group at the Rega Institute in Belgium and the U.S. biopharmaceutical company Inhibitex Inc., is soon due to complete Phase II of its clinical trials. If the drug completes Phase II, it will enter the third and final stage, and perhaps be available to patients in less than three years. Shingles is caused by the same viral infection that causes chicken pox. It is estimated that one in five people in the U.S., Europe, and Japan will be affected by the condition during their lifetime. Initial tests of FV-100 showed it has the potential to greatly reduce all of the symptoms of shingles. Previous lab research has also shown the drug to be up to 10,000 times more potent against the virus than existing treatments. Source: EurekAlert! 3/23/10

Exercise Versus Health Education to Prevent Mobility Disability in the Elderly

The University of Florida is seeking older adults between the ages of 70 and 89 to take part in a lifestyle interventions trial to determine whether exercise or health education can prevent or delay major movement disability in older adults. Field sites will be in Gainesville and Jacksonville, Fla. Little is known about whether specific interventions can help prevent major mobility disability, defined as the inability to walk a quarter of a mile, or four blocks. For older adults, staving off disability could help them maintain their physical independence and enhance the quality of their later years. The study—the largest randomized controlled trial ever conducted on physical activity in older adults—is funded by the National Institute on Aging. Called the Lifestyle Interventions and Independence for Elders, or LIFE study, it is a Phase III trial of 1,600 sedentary older adults who are at risk of mobility disability. University of Florida is one of eight institutions around the country at which the trial will be conducted. The LIFE study will compare the long-term effectiveness and practicality of two interventions: a physical activity program and a successful aging health education program. Eligible participants will be randomly assigned to take part in either a structured physical activity program that includes moderate-intensity physical activity such as walking and exercises to improve strength, balance and flexibility, or in a successful aging program that includes health education workshops and supervised stretching. Individuals will be followed for up to approximately four years. The overall trial will run for six years. For more information, click here. Source: University of Florida 3/16/10 

Thyroid Hormone Analogue for Treating High Cholesterol

An experimental thyroid drug reduces cholesterol without the troublesome side effects experienced by some people on statins, according to a study published in the New England Journal of Medicine. An international team of investigators at Johns Hopkins Medical Institutions, the Karolinska University Hospital and Institute, and The Feinstein Institute for Medical Research tested a substance called Eprotirome in patients with high cholesterol. Following 189 people with high cholesterol over a three-month period, they observed that it lowered cholesterol levels without the classic thyroid risks to the heart and bone, The study was supported by Karo Bio in Sweden, a company that is developing the drug for its cholesterol-lowering effects. In the Phase II study, the investigators reported that Eprotirome was both safe and effective in lowering cholesterol. What is not known from this study is whether this lowering of cholesterol will ultimately protect patients from heart disease. Jens Kristensen, a scientist at Karo Bio and the lead author on the study, and his colleagues found that the experimental medicine lowered a cholesterol product in the blood called lipoprotein A, which is damaging to the heart. There are no available medicines that lower lipoprotein A, and Eprotirome lowered the levels by 33 percent. Since cholesterol lowering is a surrogate marker for heart disease, the scientists will have to conduct other studies to test whether it does in fact reduce heart disease. The next phase of testing must include larger numbers of patients. If the results hold, it could ultimately be used as an alternative to statins. Source: EurekAlert! 3/11/10

Novel Stroke Treatment Passes Safety Stage of Clinical Trial

A clinical research trial of a new treatment to restore brain cells damaged by stroke has passed an important safety stage, according to the University of California Irvine neurologist who led the effort. Dr. Steven C. Cramer said patients showed no ill effects after the sequential administration of growth factors encouraging the creation of neurons in stroke-damaged areas of the brain. Results of the Phase IIa trial appear on the website of the journal Stroke. Within two days of suffering ischemic stroke, patients were put on a nine-day treatment course, starting with three once-daily injections of beta-hCG, a hormone that triggers the growth of neural stem cells. They then received three once-daily injections of erythropoietin, a hormone that directs these neural stem cells to become neurons. In the human safety study, Cramer teamed with physicians from his university's medical center, from Hoag Memorial Hospital Presbyterian in Newport Beach, Calif., and from the University of Calgary in Canada. They administered the treatment to 15 patients. No safety concerns were noted, and a majority of treated patients had minimal or no disability after three months. A Phase IIb clinical trial is now under way to compare the stroke therapy with placebo. The study is supported by Stem Cell Therapeutics--a Canadian biotechnology company that conceived of an approach using this specific sequence of growth factors--and the National Center for Research Resources. Source: EurekAlert! 3/10/10

New Drug Candidate Reduces Blood Lipids

A thyroid-hormone-like substance that works specifically on the liver reduces blood cholesterol with no serious side effects, according to a clinical trial conducted by researchers from the Swedish medical university Karolinska Institutet, among other centers. The results were published in the New England Journal of Medicine. High cholesterol levels in the blood are primarily treated with a group of drugs called statins, but they are not always sufficiently effective and higher doses commonly cause adverse reactions. A team of researchers has now shown in a clinical trial that a new drug substance called eprotirome can reduce blood cholesterol effectively in patients who have already received statins. Patients who were given supplementary medication with eprotirome demonstrated levels of harmful blood fats that were up to 30 percent lower than those of patients who received a placebo supplementary treatment. The trial lasted three months and included a total of 189 patients. It remains to be studied whether the drug candidate will be equally safe and effective for a larger group of patients over a longer period of time. "This drug could help patients who react adversely to statins or be used as a supplementary treatment for those who don't respond well to them," says Professor Bo Angelin, who led the study. Eprotirome mimics the natural ability of thyroid hormone to stimulate the metabolism of cholesterol, and exerts its effects exclusively on the liver. The development of similar nonselective drugs has previously been stopped on account of the serious adverse effects they have had on other organ systems (e.g., cardiac dilatation and osteoporosis) or on the physiological regulation of thyroid hormones. Eprotirome has been developed by pharmaceutical company KaroBio in Huddinge, which is financing and participating in the research. Source: EurekAlert! 3/10/10

Multicenter Trial to Explore Potential Benefits of Brain Cooling

Researchers at Cedars-Sinai Medical Center in Los Angeles, the University of California, San Diego (UCSD) School of Medicine, and the University of Texas Health (UTHealth) Science Center at Houston Medical School will collaborate on the largest clinical trial of hypothermia (brain cooling) for stroke to date. The single-blind, randomized, placebo-controlled ICTuS 2 study (Intravascular Cooling for Acute Stroke) is set to begin later this Spring. The three-and-a-half-year study will enroll 400 patients and is funded by two grants from the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health. A UCSD grant includes funding for 18 study sites, while a UTHealth grant will fund eight sites. Most of the sites are in the United States, but some are in Europe. Brain cooling has been shown to decrease brain swelling and reduce loss of neurologic function after an acute stroke. It has also been proven highly effective in saving lives and preventing neurologic damage after cardiac arrest and after oxygen deprivation in newborns. This trial will look specifically at whether hypothermia can be used safely in elderly stroke patients. Investigators will use an endovascular temperature modulation system from Philips Healthcare. Cooling is achieved by inserting a special catheter into the inferior vena cava. No fluid enters the patient; instead, an internal circulation within the catheter transfers heat out. Study participants are covered with a warming blanket to "trick" the body into feeling warm, and temperature sensors in the skin and a mild sedative help suppress shivering. In this study, body temperature will be cooled to 33 degrees C and maintained at that level for 24 hours. At the conclusion of the cooling period, participants will be rewarmed over 12 hours. Source: EurekAlert! 3/9/10

Acupuncture May Relieve Joint Pain from Breast Cancer Treatments

A new study led by researchers at the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian Hospital/Columbia University Medical Center demonstrates that acupuncture may be an effective therapy for joint pain and stiffness in breast cancer patients who are being treated with commonly used hormonal therapies. Results were published in the Journal of Clinical Oncology. Joint pain and stiffness are common side effects of aromatase inhibitor therapy, in which the synthesis of estrogen is blocked. The therapy, which is a common and effective treatment for early-stage, hormone-receptor-positive breast cancer in postmenopausal women, has been shown in previous research to cause some joint pain and stiffness in half of women being treated. To explore the effects of acupuncture on aromatase inhibitor-associated joint pain, the research team randomly assigned 43 women to receive either true acupuncture or sham acupuncture twice a week for six weeks. Sham acupuncture, which was used to control for a potential placebo effect, involved superficial needle insertion at body points not recognized as true acupuncture points. All participants were receiving an aromatase inhibitor for early breast cancer, and all had reported musculoskeletal pain. Among the women treated with true acupuncture, findings demonstrated that they experienced significant improvement in joint pain and stiffness over the course of the study. Pain severity declined, and overall physical well-being improved. Additionally, 20 percent of the patients who had reported taking pain relief medications reported that they no longer needed to take these medications following acupuncture treatment. No such improvements were reported by the women who were treated with the sham acupuncture. The researchers believe that this is the first randomized, placebo-controlled trial establishing that acupuncture may be an effective method to relieve joint problems caused by these medications. However, results still need to be confirmed in larger, multicenter studies. Source: EurekAlert! 3/4/10

Possible Vaccine for Mesothelioma Proven Safe

Researchers have demonstrated the safety of a potential vaccine against mesothelioma, a rare cancer associated primarily with asbestos exposure. The vaccine, which infuses uses a patient’s own dendritic cells (DC) with antigen from the patient’s tumor, was able to induce a T-cell response against mesothelioma tumors. The findings have been published online ahead of print publication in the American Journal of Respiratory and Critical Care Medicine. The anticipated increase in the incidence of mesothelioma, together with the paucity of treatment options, has spurred considerable interest in the development of new therapies. Immunotherapy, which uses the body’s own immune system to target and destroy cancer cells, has been shown to have some promise. After recruiting 10 patients recently diagnosed with malignant pleural mesothelioma of the epithelial subtype, researchers with the Erasmus Medical Center in the Netherlands cultured immature DC from their blood and exposed the DC to the antigen produced by the patients’ tumors. The DC were also exposed to keyhole limpet hemocyanin (KLH), which was used as a surrogate marker to show an immune response. The DC were then matured and injected back into the patients in three doses over a two-week interval. Serum samples from all patients showed a significant increase of pre- versus post-vaccine antibodies to KLH. In the four patients whose tumor material was sufficient for testing, there was clear induction of cytotoxicity against their own tumors after vaccination. Three patients showed signs of tumor regression, although this could not be conclusively or directly attributed to the vaccine. Source: Newswise 3/4/10

Trial Launched to Test New Treatment for Preinvasive Breast Cancer

Can a drug that has been used to treat malaria for years possibly be used to treat breast cancer before it becomes invasive? That is what researchers at George Mason University's Center for Applied Proteomics and Molecular Medicine (CAPMM) and Inova Breast Care Institute (IBCI), both in Fairfax, Va., are trying to prove. In January, the IBCI and CAPMM launched the PINC Trial (Preventing Invasive Breast Neoplasia with Chloroquine). This three-year clinical trial will test the effectiveness of the antimalarial drug chloroquine in treating 90 women with ductal carcinoma in situ (DCIS), a type of breast cancer in which the cancer cells start in the milk ducts, but have not yet become invasive and spread in the breast. Once the cancer cells start to spread in the breast and throughout the body, the condition is considered invasive and can often be fatal. According to Kirsten Edmiston, MD, the trial's principal investigator and medical director of cancer services at Inova Health System, the trial is designed to prevent breast cancer cells from becoming deadly by killing preinvasive cancer cells. "We have identified a particular cellular process called autophagy that is very involved in the survival of DCIS. In preclinical work, our team found that if we block autophagy in DCIS cells with chloroquine, that it kills the cells so that they're not able to become invasive," says Edmiston. The PINC trial will combine chloroquine with Tamoxifen, depending on the patient's tumor profile. The treatment of DCIS is controversial because most DCIS lesions remain dormant and do not become invasive. Physicians do not want to over treat DCIS and cause unnecessary side effects if the DCIS does not become aggressive. However, chloroquine is a relatively safe treatment that does not have the severe side effects of typical chemotherapy. The clinical study is being funded by George Mason University and Inova Health System, and is based on scientific findings made under a Department of Defense-funded breast cancer grant to George Mason University (Lance Liotta, MD, PhD) in partnership with Inova. Source: EurekAlert! 3/2/10

Combination Therapy More Effective for Enlarged Prostate

Like any successful team effort, the best qualities of two drugs commonly prescribed for enlarged prostate yielded better results than either of the medicines alone, according to a new study from the University of Texas Southwestern Medical Center. The findings, published in a recent issue of the journal European Urology, compared treatments for three groups of study participants with enlarged prostates over four years. The study, which included more than 4,800 men, is one of the first to compare single and combo medication regimens in such a large group. The first group of study participants received the drug dutasteride; the second group received tamsulosin; and the third received a combination of the two medicines. On the strengths of both dutasteride and tamsulosin, participants reported fewer symptoms, and researchers observed a 25 percent reduction in prostate volume. Subjects who received the combination therapy also showed a 50 percent reduction of prostate-specific antigen, a protein produced by both cancerous and noncancerous prostate tissue. Compared to tamsulosin alone, the combination of drugs reduced the incidence of acute urinary retention by 67 percent and reduced the need for benign prostatic hyperplasia-related surgery by 70 percent. Other researchers contributing to the study were from the Deaconess Clinic in Evansville, Ind.; State University of Rio de Janeiro; Universita Vita Salute San Raffaele, Italy; University of Toronto; and GlaxoSmithKline, which funded the study. Source: EurekAlert! 3/2/10

Medical School and Hospital Team Up for New Initiative

The Wright State University Boonshoft School of Medicine and Miami Valley Hospital, both in Ohio, announced in February the formation of the Wright State University & Premier Health Partners Neuroscience Institute to speed the transfer of research discoveries from bench to bedside. The public-private initiative partners a biomedical research institution with the clinical resources of a hospital system. Miami Valley Hospital has made a major investment of $4.35 million over five years to create a new Department of Neurology within the university's medical school. The investment includes long-term support for clinical neurologists who will form the nucleus for collaboration with the university-based neuroscientists in critical research in stroke and movement disorders. A national search is under way for the founding chair of the new department. The announcement from the university and hospital system cites the partnership's committment to "investing significant fiscal resources to recruit new physician-scientists to join our talented faculty in the institute, with the goal of providing improved neurological care for our community as well as longer-term clinical trials and continuing research." Source: PRNewswire 2/24/10

Traumatic Brain Injury Study to Use Exception from Informed Consent Provision

Penn State Milton S. Hershey Medical Center is seeking public comment on its participation in a national research study evaluating the use of a hormone during a traumatic brain injury. Because the patients eligible for this study are unable to provide informed consent before receiving the study medication, this study will be conducted under federal regulations that allow for clinical research in emergency settings using an exception from the requirement for informed consent (21 CFR 50.24). Progesterone for the Treatment of Traumatic Brain Injury, or ProTECT, is studying the use of progesterone, a steroidal hormone found naturally in the body, to limit the damage caused during brain injury. There is currently no drug treatment for traumatic brain injury; instead doctors attempt to control blood pressure and oxygen levels to minimize damage. Patients 18 years and older with a blunt, closed head injury, with moderate to severe brain injury, and who can receive the study medication within four hours from the time of injury are eligible for this study. Upon arrival at the hospital, patients will be randomly entered into the study, receiving either an IV mixture that includes progesterone, or one that does not (a placebo). Both sets of patients will receive standard medical care for a brain injury. Participation in the study includes receiving the study medication or placebo, blood tests, receiving calls once per month for five months, and a clinic visit the sixth month to take a series of paper and pencil tests. Use of the exception from informed consent provision in a study protocol is granted by the institutional review board responsible for the initial and continuing review and approval of the research study. Such a decision is based on the finding and documentation that, among other things, patients are in a life-threatening situation requiring emergency medical intervention, currently available treatments are unproven or unsatisfactory, obtaining informed consent is not feasible, potential risks are reasonable in relation to what is known of the condition, participation in the study could provide a direct benefit to the patients enrolled, and the research could not be practicably conducted without an exception from informed consent requirements. Upon arrival at the medical center, study team members will try to locate a legally-authorized representative for one hour to get permission to enter the patient into the study. If a representative cannot be located, study medication or placebo will be started after one hour. Once located, if the representative does not give permission, the study medicine will be no longer administered to the patient. In addition, the public can request opt out bracelets. These bracelets alert study personnel that a patient is not to be entered into the study. Bracelets must be worn at all times throughout the study period, estimated at about four years. In addition, residents can add their names to a national opt-out database. Source: Penn State Live 2/17/10

Miniature Ultrasound Device Could Revolutionize Pain Relief

It looks more like an iPod than a medical tool, but the latest miniature ultrasound device created by Cornell biomedical engineering graduate student George K. Lewis could one day introduce a whole new level of home therapy for arthritis, injury, and other painful ailments. The sleek, blue-and-white device slips into a pocket and sends ultrasound waves deep into muscles via a coin-sized polystyrene pad. This is the transducer, which converts electrical energy into ultrasound. Lewis hopes that this model--possibly the world’s smallest ultrasound device--can hit the marketplace and find itself in the pockets of millions of people. To give his work medical legitimacy, Lewis has partnered with Cary Reid, a geriatrician at Weill Cornell Medical College’s Irving Sherwood Wright Center on Aging, and Charles Henderson, senior research associate in the Department of Human Development, to prepare a clinical trial that will focus on osteoarthritis patients to determine whether the devices can significantly reduce joint pain. Lewis’ latest prototype sends low-intensity energy in the form of ultrasound waves from the transducer into the body at a level that is gentle enough for the device to be kept close to the skin for up to 10 hours. The clinical study at Weill Cornell will be restricted to patients with osteoarthritis of the knee. Reid emphasized that for the study to be successful, participants must not only experience reduced pain, but also increased mobility. Among other uses, Lewis hopes his device can also affect treatment for the brain cancer glioblastoma. After tumor removal surgery, a surgeon would place a dissolving drug wafer into the hole, and the ultrasound would help spread the drug to kill the remaining cancer. However, to make new claims and get Food and Drug Administration approval will require additional clinical studies down the road, Lewis said. His research is supported by the National Science Foundation. Source: Newswise 2/17/10

First FDA-Approved Stem Cell Trial Under Way in Pediatric Cerebral Palsy

Medical College of Georgia (MCG) researchers are conducting the first Food and Drug Administration (FDA)-approved clinical trial to determine whether an infusion of stem cells from umbilical cord blood can improve the quality of life for children with cerebral palsy. The study will include 40 children age 2-12 whose parents have stored cord blood at the Cord Blood Registry in Tucson, Ariz. Umbilical cord blood is rich in stem cells, which can divide and morph into different types of cells throughout the body, said Dr. James Carroll, professor and chief of pediatric neurology in the MCG School of Medicine and principal investigator on the study. While no controlled clinical trials have been conducted to date, previous studies have shown marked improvement in children with cerebral palsy about three months after an initial infusion of cord blood. Children will begin the study with a neurological exam. Then, half of the study participants will receive an infusion of their own cord blood while the other half receive a placebo. Three months later, the children will be evaluated without physicians knowing which group received the stem cell infusion. Afterward, children who did not get the cord blood initially will receive an infusion. Children will return three and six months later for evaluation. Researchers will periodically assess the children's motor skills and neurological development. The trial is also receiving support from the Associazione Figli Inabili Banca d'Italia, a private organization in Italy that provides financial assistance to parents who cannot pay for their children's medical treatments. Source: EurekAlert! 2/11/10 

Direct-Injection Vaccine Combo Tested for Pancreas Cancer

Researchers at the Cancer Institute of New Jersey (CINJ) are investigating the development of a series of vaccine injections to see if they will produce an immune response against pancreatic cancer. CINJ is a Center of Excellence of the University of Medicine and Dentistry of New Jersey (UMDNJ)-Robert Wood Johnson Medical School. It has been known for a number of years, based on studies by scientists at CINJ and elsewhere, that the presence of a tumor in the body can actively inhibit the immune system from recognizing and destroying these same tumors. Studies on mouse models at CINJ have shown this blockade of immunity also prevents traditional cancer vaccines from producing a good response. As part of these studies at CINJ, investigators have shown that injecting a vaccine and other immunity-producing drugs into the tumor itself--rather than the traditional site of the skin--can result in a reversal of the immune blockade and the development of specific immunity to the tumor. This body-wide tumor-specific immunity has the potential of inhibiting the growth of the original tumor as well as eliminating small deposits of tumor that can form metastases. These findings have led to the development of a vaccine strategy targeting patients with pancreatic cancer, where the vaccine would be injected directly into the tumor. It is believed that this trial would be the first such study to evaluate direct injection into a pancreas tumor to enhance the body’s immune response to help fight the cancer. Elizabeth Poplin, MD, medical oncologist at CINJ and professor of medicine at UMDNJ-Robert Wood Johnson Medical School, is the lead researcher on this clinical trial sponsored by the National Cancer Institute, which will look at the investigational vaccine known as PANVAC. PANVAC has special genes added to it that might stimulate a person’s immune system to recognize and develop an immune response to the disease. Two types of PANVAC will be utilized in the two-year study, which will test approximately a dozen patients whose pancreatic cancer cannot be removed through surgery. PANVAC-V, which uses the same virus as the smallpox vaccine, is a live but weakened vaccinia vaccine (meaning the virus can still multiply) that will be given in the arm. PANVAC-F (a live Fowlpox virus that cannot multiply) would be injected into the arm and into the tumor itself. Direct tumor injection would take place through a procedure known as endoscopic ultrasound, in which a scope is inserted through the mouth and into the stomach. From inside the stomach, the pancreas can be seen clearly, allowing injection of the vaccine into the tumor. Source: Newswise 2/10/10 

Medication Appears Well-Tolerated, Beneficial in Huntington's Disease Patients

A medication previously studied in patients with Alzheimer's disease (latrepirdine) appears well tolerated and may improve thinking, learning, and memory skills among individuals with Huntington's disease, according to a report in the February issue of Archives of Neurology. Abnormalities in mitochondria, parts of cells that help convert food into energy, have been implicated in the development of Huntington's disease. The synthetic molecule latrepirdine stabilizes and improves mitochondrial function, and has been studied as a way to improve cognitive, behavioral, and functional outcomes in patients with Alzheimer's disease. Karl Kieburtz, MD, MPH, of the School of Medicine and Dentistry, University of Rochester, N.Y., and colleagues assessed the safety and tolerability of latrepirdine among 91 participants with mild to moderate Huntington's disease at enrollment (2007 to 2008). For 90 days, 46 patients were randomly assigned to take 20 mg of latrepirdine three times daily and the other 45 took a matching placebo. The medication was well tolerated (87 percent of the patients given latrepirdine completed the study, compared to 82 percent in the control group) and adverse event rates were similar between the two groups (70 percent in the treatment group versus 80 percent in the placebo group). In addition, the treatment resulting in improved average scores on an evaluation measuring overall cognitive function. Scores of individuals in the placebo group remained steady over the study period. The study was funded by a grant from Medivation Inc., which is developing the drug under the name Dimebon, to the University of Rochester and in turn through subcontracts to the participating research sites. The drug is also being testing in patients with Alzheimer's disease. In July of last year, Medivation and Pfizer, Inc. launched a Phase III clinical trial of the drug for Huntington's disease. The study, called the Horizon Trial, is being conducted in sites throughout North America, Australia, and Europe. Kieburtz is the principal investigator of the Horizon Trial. Sources: EurekAlert! 2/8/10 and EurekAlert! 2/8/10 

New Malaria Vaccine Found to be Safe, Promotes Immune Response in Children

A new vaccine to prevent the deadly malaria infection has shown promise to protect the most vulnerable patients—young children—against the disease, according to an international team of researchers led by the University of Maryland School of Medicine's Center for Vaccine Development (CVD) and the Malaria Research and Training Center at the University of Bamako in Mali, West Africa. In a new study of the vaccine in young children in Mali, researchers found it stimulated strong and long-lasting immune responses. In fact, the antibody levels the vaccine produced in the children were as high or even higher than the antibody levels found in adults who have naturally developed protective immune responses to the parasite over lifelong exposure to malaria. "These findings imply that we may have achieved our goal of using a vaccine to reproduce the natural protective immunity that normally takes years of intense exposure to malaria to develop," says Christopher V. Plowe, MD, MPH, professor and chief of the Malaria Section of the CVD. Dr. Plowe, a lead author of the study published online in the February 4 issue of PLoS ONE, also is an investigator with the Howard Hughes Medical Institute and a Doris Duke Distinguished Clinical Scientist. In addition to the Howard Hughes Medical Institute's support of Dr. Plowe's research, the study was sponsored by the U.S. Army and funded by the National Institute of Allergy and Infectious Disease, part of the National Institutes of Health, and the United States Agency for International Development. The new vaccine, called FMP2.1/AS02A, was developed as part of a longstanding research collaboration between the Walter Reed Army Institute of Research and GlaxoSmithKline Biologicals, and targets malaria in the blood stage. For the study, the University of Maryland School of Medicine's CVD team collaborated with a group of Malian researchers from the Malaria Research and Training Center, led by Mahamadou Thera, MD, PhD, and Ogobara Doumbo, MD, PhD. The scientists tested the vaccine in 100 Malian children ages 1-6 at the Bandiagara Malaria Project in rural Mali. The children were randomly assigned to receive either one of three escalating doses of the malaria vaccine or a control rabies vaccine. All three doses of the vaccine proved to be safe and well tolerated, and all three doses also showed very strong antibody responses that were sustained for at least a year. Based on the vaccine's apparent success in this early trial, the same international team of U.S., Malian, and European investigators now are subjecting it to further study in a much larger trial of 400 Malian children to evaluate its effectiveness against malaria disease. That study also will examine whether the vaccine—though it is based on a single strain of malaria—can protect against the broad array of malaria parasites that exist. The scientists hope the vaccine could be combined with other vaccines to create a multicomponent immunization that is highly protective. Source: EurekAlert! 2/3/10 

New Vaccine Effective in Preventing TB in African Patients with HIV Infection

Investigators from Dartmouth Medical School have reported results of a clinical trial showing that a new vaccine against tuberculosis, Mycobacterium vaccae (MV), is effective in preventing tuberculosis in people with HIV infection. The DarDar Health Study, named for Dartmouth and Dar es Salaam, Tanzania, found that MV immunization reduced the rate of definite tuberculosis by 39 percent among 2,000 HIV-infected patients in Tanzania. The study appears in the January 29 online issue of the journal AIDS, and it will be published in the March print issue. The seven-year, randomized, placebo-controlled trial was conducted in Tanzania with collaborators at the Muhimbili University of Health and Allied Sciences in Dar es Salaam, and was supported by a grant from the National Institutes of Health in the United States. Source: EurekAlert! 1/29/10 For more information in the ACRP Wire, click here.

Federal Grant Funds Production of Stem Cells for Clinical Trials

Efforts to move the most versatile stem cells from the laboratory to the clinic have received another boost with an $8.8 million contract award to the Waisman Clinical Biomanufacturing Facility at the University of Wisconsin-Madison. The facility contains a series of clean rooms that can manipulate and produce biological products that are pure enough to be used in human therapies. "Our main function is to understand how to manufacture biological products and biotechnology drugs in a way that can go into human clinical trials," says Derek Hei, a biochemical engineer who is the facility's technical director. "We also help investigators follow and interpret Food and Drug Administration rules as they move into clinical trials." The contract, announced in January by the National Heart, Lung, and Blood Institute, will support research at the university and researchers and firms around the nation. Source: EurekAlert! 1/26/10

Medical Center Leads Nationwide Trial of Nutritional Drink for Alzheimer's

Rush University Medical Center is leading a nationwide clinical trial of a nutritional drink to determine whether it can improve cognitive performance in people with mild to moderate Alzheimer's. The study follows recently released results from an earlier trial conducted in Europe showing that the drink, called Souvenaid, improved verbal recall in people with mild disease who were followed for three months. "Our primary goal is to see whether Souvenaid can slow the worsening of memory difficulties in persons with mild to moderate Alzheimer's who are already taking approved treatments for the disease, " said Dr. Raj Shah, medical director of the Rush Memory Clinic and one of the study's lead investigators. A total of 500 individuals who are taking medications approved by the U.S. Food and Drug Administration for the symptomatic treatment of mild to moderate Alzheimer's disease will be enrolled in the present study at 40 sites across the U.S. In the double-blinded study, half of the participants will drink about four ounces of Souvenaid once a day for 24 weeks. The other half will drink a control product that is similar in flavor, appearance, and composition, but without the Souvenaid nutrients. Neither group will know whether they are drinking Souvenaid or the other beverage. Researchers will test whether the participants' cognitive and functional performance—including memory, language, attention/concentration, executive functioning, information processing and recall—shows any greater improvement with Souvenaid than with medication alone. Rush University Medical Center receives payment from Nutricia for conducting the trial. Source: EurekAlert! 1/25/10

First Evidence that Blueberry Juice Improves Memory in Older Adults

Scientists are reporting the first evidence from human research that blueberries—one of the richest sources of healthful antioxidants and other so-called phytochemicals—improve memory. They said the study establishes a basis for comprehensive human clinical trials to determine whether blueberries really deserve their growing reputation as a memory enhancer. A report on the study appears in the Journal of Agricultural and Food Chemistry. In the study, one group of volunteers in their 70s with early memory decline drank a commercially available blueberry juice every day for two months. A control group drank a beverage without blueberry juice. The blueberry juice group showed significant improvement on learning and memory tests, the scientists say. "These preliminary memory findings are encouraging and suggest that consistent supplementation with blueberries may offer an approach to forestall or mitigate neurodegeneration," said the report. The research involved scientists from the University of Cincinnati, the U.S. Department of Agriculture, and the Canadian department of agriculture. Source: EurekAlert! 1/20/10

Academic-Industry Collaboration for Drug Discovery in Depression and Schizophrenia Launched

An international consortium of scientists, led by H. Lundbeck A/S and King's College London, has launched one of the largest ever research academic-industry collaboration projects to find new methods for the development of drugs for schizophrenia and depression. Novel Methods leading to New Medications in Depression and Schizophrenia (NEWMEDS) is a unique project, bringing together top scientists from academic institutions with a wide range of expertise and partnering them with nearly all major global drugs companies, including AstraZeneca, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutica, Novartis, Orion, Pfizer, Roche, Servier, and Wyeth. Other academic institutions involved are Karolinska Institutet (Sweden), the University of Cambridge (United Kingdom), Central Institute of Mental Health (Germany), CSIC (Spain), the University of Manchester (United Kingdom), and the Bar Ilan University (Israel). A further two pharmaceutical small and medium-sized enterprises, deCODE (Iceland) and Psynova (United Kingdom), will contribute to the success of NEWMEDS, while GABO:mi (Germany) will manage the project. With a wealth of new knowledge and research findings related to schizophrenia and depression emerging every year, it has been hard to take these findings from the bench to the clinic. The researchers believe there to be three major bottlenecks that are holding the field back: a lack of accurate animal models to guide the drug discovery, a lack of tools and tests in healthy volunteers that can provide early indication of efficacy, and the reliance of clinical trials on symptom-based Diagnostic and Statistical Manual categories, which inevitably leads to biologically heterogeneous groups of patients. NEWMEDS aims to overcome these limitations with a novel approach to drug discovery and strong collaboration within the consortium, including a focus on developing new approaches for shorter and more efficient trials of new medications—trials that may require fewer patients and give faster results. Source: EurekAlert! 1/15/10

Investigational Drug May Minimize Death and Disability from Traumatic Brain Injury

A clinical trial of a new neuroprotective drug for people with traumatic brain injuries will be offered to patients seen in the University of California Davis Medical Center's level-1 trauma center, through an $8 million grant funded by the Congressionally Directed Medical Research Program of the U.S. Department of Defense. The study's primary aim is to determine whether the drug, a neuroactive steroid called allopregnanolone, would be an effective treatment for severe brain injuries, such as those occurring in car crashes, sports and recreation accidents, and falls. Active duty military personnel in war zones also experience severe brain injury as a result of blasts from the explosion of makeshift bombs or improvised explosive devices. The study will take place over five years, and will be led by Michael Rogawski, professor and chair of the Department of Neurology at the university's medical school. All 18-to-59 year-old patients with severe blunt or penetrating head trauma seen at the medical center's emergency department will be approached to participate in the clinical trial. Patients who enroll will receive either allopregnanolone or a placebo within hours of a brain injury and at regular intervals over a five-day period. Researchers hope to enroll 136 male and female patients to determine whether receiving the drug minimizes brain damage, reduces or eliminates post-traumatic epileptic seizures, and improves patients' psychological functioning and overall quality of life. The university is sponsoring the trial as well as manufacturing the drug. Source: EurekAlert! 1/15/10

Novel Personalized Medicine Trial Launched for Metastatic Colorectal Cancer

Imagine if treatments for disease could be based not on a patient's diagnosis but instead on the characteristics of their tissue. By identifying and decoding the cryptic messages hidden deep inside the human proteome, scientists and physicians who study personalized medicine are seeking more effective treatments and disease management for patients. Lance Liotta, MD, and Emanuel Petricoin, III, professors of life sciences and codirectors of George Mason University's Center for Applied Proteomics and Molecular Medicine in Fairfax, Va., are pioneers in the field of patient-tailored research and personalized medicine. The two are studying biomarkers (or indicators of disease in tissue and bodily fluids) related to cancer, heart disease, liver disease, and obesity. They recently launched a unique clinical trial in partnership with oncologists and coprincipal investigators Kirstin Edmiston, MD, medical director of cancer services at Inova Health System, and Alexander I. Spira, MD, director of Fairfax Northern Virginia Hematology Oncology Research Program, to treat patients with late-stage colorectal cancer, a fatal cancer that starts in either the colon or the rectum. The three-year trial will accommodate up to 50 men and women who have late-stage colorectal cancer that has spread to the liver. Trial participants will be treated with standard metastatic colon cancer therapy with the addition of Gleevec, a medicine that is typically prescribed for certain forms of leukemia and gastrointestinal tumors. Gleevec targets disease pathways in tumor cells that previous research revealed were among those found in typically fatal liver metastasis in colorectal cancer patients. Because the primary tumors in the colon are removed in most colorectal cancer patients as soon as they are diagnosed, this study will focus on treating the often fatal secondary tumors or metastatic lesions that appear when the disease spreads to the liver, causing death through destruction of that organ. This is the first trial that uses a direct proteomic approach that maps the drug target activation networks that are in use in each patient's tumor. Financial support for the study is being provided by Novartis, which developed and manufactures Gleevec. Source: EurekAlert! 1/15/10

Researchers Launching Trial of New Osteoporosis Drug

Endocrinologists at the University of Pittsburgh School of Medicine and University of Pittsburgh Medical Center are launching a human trial of a new drug that their research indicates holds great promise for building bones weakened by osteoporosis. For the study, 105 participants will be randomly assigned to receive either teriparitide (Forteo®), a drug that already is approved by the Food and Drug Administration for osteoporosis treatment, or an experimental agent called parathyroid hormone-related protein (PTHrP), explained principal investigator Mara J. Horwitz, MD, an assistant professor of medicine in the Division of Endocrinology and Metabolism and a practicing metabolic bone specialist. PTHrP, a protein made naturally by the body, is an anabolic agent and appears to be unique in its ability to stimulate bone formation without simultaneously increasing bone breakdown. Both PTHrP and teriparitide are given as daily injections. In findings published online recently in the Journal of Clinical Endocrinology and Metabolism, Horwitz and other researchers identified the maximum tolerable dose and therapeutic window of PTHrP, and were able to show that PTHrP, at the tolerable doses, stimulated bone formation after only three weeks of treatment. The research was funded by the National Institutes of Health and the University of Pittsburgh Clinical Translational Sciences Award. Source: EurekAlert! 1/14/10

Startup to Begin Clinical Trials for Wireless Body-Monitoring System

MediSens Wireless, a startup company in the University of California, Los Angeles (UCLA) on-campus technology incubator at the California NanoSystems Institute, has obtained approval under federal Food and Drug Administration guidelines to begin clinical trials on its novel wireless body-monitoring system, which assesses muscle and neuromotor functions in the upper extremities. The Clinical Movement Assessment System (CMAS) is designed for a wide variety of medical applications and could potentially benefit healthcare professionals and facilities specializing in the areas of physical medicine and rehabilitation, neurology, orthopedics, and physical and occupational therapy, among others. The CMAS system consists of a clinical assessment device and associated software that will allow healthcare providers to capture current and ongoing muscle and neuromotor functions, thereby providing them with quantifiable, real-time data for their decision-making. Clinical trials will establish the viability of CMAS. It is anticipated that the system will provide clinical assessments of fine motor movement, gross muscle strength, hand-eye coordination, and patient response to treatment. Closely captured repeat assessments will lead to early warning and detection of deteriorating conditions. According to MediSens' medical director, Dr. Nick Terrafranca, DPM, the trials are planned as a multicenter, multidiscipline study that will involve community hospitals and public health facilities, as well as the Ronald Reagan UCLA Medical Center. The first phase of the trial will deal with baseline evaluations and therapeutic exercise. The second phase will involve an in-depth analysis of different sensory-motor pathways. The success of the trial will be evaluated by the efficacy and cost effectiveness of the system in testing early interventions for better outcomes and long-term patient care. Source: EurekAlert! 1/12/10

New Approach to Fighting Alzheimer's Shows Potential in Clinical Trial

In the early stages of Alzheimer's disease, patients typically suffer a major loss of the synapses necessary for memory and information processing. Now, a combination of nutrients that was developed at MIT has shown the potential to improve memory in Alzheimer's patients by stimulating growth of new brain connections. In a clinical trial of 225 Alzheimer's patients, researchers found that a cocktail of three naturally occurring nutrients believed to promote growth of synapses, plus other ingredients (B vitamins, phosopholipids, and antioxidants), improved verbal memory in patients with mild Alzheimer's. A paper describing the results appears in the journal Alzheimer's and Dementia. The three nutrients in the dietary cocktail—uridine, choline, and the omega-3 fatty acid DHA (all normally present in breast milk)—are precursors to the fatty molecules that make up brain cell membranes, which form synapses. In animal studies, these nutrients boost the number of dendritic spines (small outcroppings of neural membranes). When those spines contact another neuron, a synapse is formed. Three additional clinical studies in Alzheimer's patients are now under way in the United States and Europe. Results are expected to be available between 2011 and 2013. The first clinical study was sponsored by the French company Danone, known in the United States as Dannon; the study was conducted primarily in Europe. Patients with mild Alzheimer's drank the cocktail (made in the form of a nutrient drink called Souvenaid, with the collaboration of Danone) or a control beverage daily for 12 weeks. Patients who received the nutrients showed a statistically significant level of improvement compared to control subjects: 40 percent of the treated patients improved performance in a test of verbal memory (memory for words, as opposed to memory of locations or experiences), while 24 percent of patients who received the control drink improved their performance. Among those who received the cocktail, patients with the mildest cases of Alzheimer's showed the most improvement. Source: EurekAlert! 1/8/10

Medical Center Testing Gene Therapy for Alzheimer's Disease

University Hospitals Case Medical Center is one of 12 sites conducting the first Phase II clinical trial of a gene therapy for Alzheimer's disease. The study uses a viral-based gene transfer system called CERE-110, which is designed to deliver nerve growth factor into the brain. The study is sponsored by a contract to Case Western Reserve University from the Alzheimer's Disease Cooperative Study through a grant from the National Institute on Aging in association with Ceregene, Inc., which developed and will provide the active agent CERE-110. During the study, CERE-110 will be injected by a neurosurgeon into the nucleus basalis of Meynert, an area of the brain where nerve cells die in patients with Alzheimer's. The Phase II study follows up on a smaller study in humans to evaluate whether the therapy is safe for a larger group of patients and whether it helps the symptoms of the disease. In total, 50 patients will be enrolled throughout the United States and University Hospitals aims to enroll at least five patients in this study. Participants will be randomly placed into one of two treatment groups, with half of the subjects receiving CERE-110 and the other half receiving placebo surgery. At the completion of the trial, subjects in the placebo arm may have the opportunity to receive the active treatment if the product seems safe and effective. Source: EurekAlert! 1/7/10

Electric Field Propels Worms to Test New Drugs

A Nobel-winning process for testing new drugs to treat diseases such as Huntington's, Parkinson's, and muscular dystrophy is getting an electrical charge. Researchers at McMaster University have developed a way to propel and direct microscopic-sized worms (C. elegans nematodes) along a narrow channel using a mild electric field. The discovery opens up significant possibilities for developing high-throughput micro-screening devices for drug discovery and other applications. "This is the first time that worms have been stimulated to move in a micro-channel device in a very precise and directed way," said Bhagwati Gupta, assistant professor of biology. "It will allow researchers to study in real time how a proposed drug affects neurons and muscles that control motion of a live specimen." The research is described in the January 21 issue of Lab on a Chip. The researchers demonstrate movement of the worms forward and in reverse inside a microchannel, guided by the direction of the electric field (electrotaxis). "The electrotaxis of the worms has the potential to automate what is currently a slow, manual process for drug screening on worms," said Ravi Selvaganapathy, assistant professor of mechanical engineering. "The system is fairly easy and inexpensive to scale up to conduct rapid screening of tens of thousands of chemicals in worms to identify drug candidates in a cost-effective manner. Such discovery could accelerate clinical trials in people by allowing scientists to focus only on relevant drugs and would use limited resources more efficiently." Currently, researchers observe worms individually under a microscope as they move in a random manner or in a direction forced by pressure. The new development retains a worm's natural motion and causes no harm to the worm. Source: EurekAlert! 1/5/10

St. John's Wort Not Helpful for Irritable Bowel Syndrome

A Mayo Clinic research study published in the January issue of the American Journal of Gastroenterology found that St. John's wort is not an effective treatment for irritable bowel syndrome (IBS). In the placebo-controlled trial, 70 participants with IBS were randomized where half the patients received St. John's wort and the other half received a placebo for three months. In all, 86 percent of the participants were women, and the median age was 42 years. After three months of observing such symptoms as stomach pain, diarrhea, constipation, and bloating, the researchers found that the placebo group had a better response than the group taking the herbal supplement. St. John's wort has been shown to be helpful in several medical conditions, including depression and pain syndromes; research has shown it to be as effective as conventional, prescription antidepressants in treating mild to moderate depression. Source: EurekAlert! 1/4/10

Potential New ALS Drug Completes Phase II Trial

A drug already used to treat symptoms of epilepsy has potential to slow the muscle weakening that comes with amyotrophic lateral sclerosis (ALS), scientists reported after completing a Phase II clinical trial. A report online December 4 in the journal Amyotrophic Lateral Sclerosis says the drug talampanel showed some ability to slow the loss of such major daily life activities as speaking, walking, and dressing, which typically slip away as the disease progresses. The drug is a member of the benzodiazepine family—anti-anxiety and muscle-relaxing agents that work in the brain and spinal cord. The study, by a scientific team from Johns Hopkins and Indiana University, reveals that there is enough benefit from this new use of talampanel to propel it into larger trials that will definitively tell its worth. The trial in 59 volunteers with ALS—also called Lou Gehrig's disease—showed that talampanel can be safe for patients with the disease and that any recorded side effects are tolerable. The drug's effect on ALS symptoms was not overwhelming at the dosage of medicine used in the very small trial; ALS patients in the talampanel-receiving group (40 of the 59) at both Johns Hopkins and Indiana University took a month to ease into the trial-desired dose of the drug, and most stayed there for the remaining eight months of the study. Periodically, clinicians rated the 40 who got talampanel and the 19 control subjects on a measure of isometric arm muscle strength. Testing also included the rate of decline in breathing and the ALS Functional Rating Scale—a standard measure of abilities that include speech, swallowing, handwriting, breathing, walking, and food cutting. In most cases, talampanel slowed progression of ALS. Results stood out, especially, in the rating scale, where patients' decline in abilities slowed by 30 percent. A large international trial of talampanel is now under way and due to end in 2010. The just-completed trial was funded and organized by Lilly Pharmaceuticals, which manufactures the drug. Source: EurekAlert! 1/4/10

Clinical Trial Seeks to Improve Patient Treatment for Crohn’s Disease

Robarts Clinical Trials at the University of Western Ontario in London, Canada, has been awarded a $4.7 million grant to conduct a randomized controlled trial evaluating treatment options for Crohn's disease. The outcome is expected to lead to a more streamlined treatment path and better disease management for patients. Abbott, the global healthcare company, has provided a grant to complete research for the REACT (Randomized Evaluation of an Algorithm for Crohn's Treatment) study. The study will be carried out at 40 gastroenterology practices in Canada and Belgium. The sites will be randomly assigned to treat patients with Crohn's disease to either a conventional management strategy featuring gradual escalation of drug therapy or a newer paradigm that features early use of combined immunosuppression with a tumor necrosis factor alpha blocking drug and an antimetabolite. "This trial builds on the results of recent studies that suggest use of combined therapy early in the course of treatment yields superior long-term results," says Dr. Brian Feagan, the lead investigator for the study. "We are excited about this project since it is the first large-scale, community-based evaluation of this approach. We expect that patients treated with combination therapy will be more likely to enter remission and rates of hospitalization and healthcare utilization will be reduced." Source: EurekAlert! 1/4/10

Novel Anti-Epilepsy Drug to Begin Clinical Trials

A sugar-like substance used for years in medical imaging is about to be tested in clinical trials to see if it can protect people who suffer from frequent epileptic seizures. The compound, known as 2-deoxy-D-glucose (2DG), seems to trick the body into believing there is no sugar available, thus mimicking the effect of a ketogenic or no-sugar diet in reducing seizures. Clinical trials on epilepsy patients are expected to begin in 2010 at the University of Virginia. University of Wisconsin neurology researchers Avtar Roopra, PhD, Thomas Sutula, MD, PhD, and Carl Stafstrom, MD, PhD, reported the novel anticonvulsant and disease-modifying effects of 2DG on animals with a type of epilepsy in the journal Nature Neuroscience in 2006. "It's very gratifying to see this discovery go from the lab to being tested in patients," said Sutula. The hope is that 2DG can be used to treat the 30 percent of patients whose seizures are not controlled by current drugs. By blocking the metabolism of sugar, 2DG suppresses excitability in the brain leading to seizures, and also favorably modifies expression of neural genes. "Not only does 2DG have anticonvulsant effects, it is very unique in that it can be given with increased effectiveness right after a seizure," Sutula said. The Wisconsin researchers patented 2DG for its use against epilepsy in collaboration with the Wisconsin Alumni Research Foundation, forming the Madison company NeuroGenomeX, Inc. The trial is being funded by the Epilepsy Research Foundation and the Epilepsy Therapy Development Project, and through efforts of Neurogenomex and WARF. Dr. Nathan Fountain, head of the F.E. Dreifuss Comprehensive Epilepsy program at the University of Virginia, is expected to begin recruiting patients for the trial in early 2010. Source: University of Wisconsin press release 12/28/09

Anemia Drug Not Helpful for Kidney Disease Patients

An international study authored by a University of Texas (UT) Southwestern Medical Center researcher has concluded that the anemia drug darbepoetin alfa works no better than a placebo in several other applications previously thought to be promising. Darbepoetin alfa is one of a class of drugs used to increase red blood cells in patients with Type 2 diabetes, chronic kidney disease, and anemia, but in a study of 4,038 patients, it did little to reduce cardiovascular problems, death, or even the need for dialysis. Patients have used the drug and other similar drugs for at least a decade to improve the symptoms of anemia. "We were disappointed that the drug didn't make a difference," said Dr. Robert Toto, professor of internal medicine and senior author of the study in the New England Journal of Medicine. "We set out doing this trial to prove whether treatment of anemia would help our patients." Researchers also found that subjects who took the drug were nearly twice as likely to have a stroke as those who received a placebo--101 subjects compared to 53. While studies have been done in an attempt to determine optimal hemoglobin levels using the drug, no trial was conducted comparing it with a placebo, until TREAT (Trial to Reduce Cardiovascular Events with Aranesp Therapy), which was a randomized, double-blind, placebo-controlled study. From August 2005 until March 2009, researchers from 24 countries gave subjects with chronic kidney disease, Type 2 diabetes, or anemia either a placebo or darbepoetin alfa. Twenty-four subjects were from UT Southwestern. Cardiac death or events occurred in 31 percent of the darbepoetin alfa group and in 29 percent of the placebo group. Kidney disease death or progression to dialysis occurred in 32 percent of the darbepoetin alfa group and in 31 percent of the placebo group. Researchers did find a modest decrease in reported fatigue levels and a decrease in the need for blood transfusion in subjects taking darbepoetin alfa. Also involved in the study were researchers from Harvard Medical School; Tufts Medical Center in Boston; Hospital de Base, Faculdade de Medicina de São José do Rio Preto in Brazil; Amgen in California; Baker Heart Research Institute in Australia; University Medical Center in the Netherlands; University of Erlangen-Nuremberg in Germany; University of Wisconsin; Northwestern University Feinberg School of Medicine; Washington University School of Medicine; British Heart Foundation Glasgow Cardiovascular Research Centre; St. John's Health Sciences Centre in Canada; University of Copenhagen and Aarhus University in Denmark; and Mario Negri Institute for Pharmacological Research in Italy. The study was funded by Amgen. Dr. Toto has received consulting fees and lecture fees from Amgen and grant support from Novartis, Reata, and Abbott. Source: EurekAlert! 12/22/09

Translational Science Institute Announces Organizational Changes

The Wake Forest University Translational Science Institute has announced a number of organizational changes. Four programs and four specialized centers have been organized to function collaboratively in support of research conducted at Wake Forest University Baptist Medical Center. The institute's mission is to generate and “translate” biomedical science and knowledge into improved healthcare. “To best support this mission, the Wake Forest Baptist leadership is committed to building an infrastructure that facilitates and supports the clinical and translational research initiatives within our institution, with our academic partners and our community collaborators,” said Charles E. “Cash” McCall, MD, director of the institute and professor of translational science. The four specialized programs are the Clinical & Translational Research Facilitation Program (with a newly developed Clinical Trials Office), the Community Engagement & Implementation Program, the Innovation & Technologies Program, and the Translational Research Academy. The four specialized centers are Biomedical Research Informatics, Primate Models of Chronic Diseases, Genomics & Personalized Medicine, and Population Science & Research Design. Source: Newswise 12/17/09

Universities Launch Joint Center for Translational Medicine

The California Institute of Technology (Caltech) and the University of California, Los Angeles (UCLA) have announced the establishment of the Joint Center for Translational Medicine, which will advance experimental research into clinical applications, including the diagnosis and therapy of diseases such as cancer. Initial funding for the new center comes from a two-year, $5 million gift from the Eli and Edythe Broad Foundation. The first project of the center will be the investigation into a potentially revolutionary treatment for late-stage melanoma, in which the body's killer immune cells are programmed to recognize and destroy tumor cells. This work started in 2006 as joint research between Caltech and UCLA and led to the idea for the center. The melanoma research has already advanced to ongoing clinical trials involving a half-dozen patients. The center also will immediately begin a Translational Acceleration Grants (TAG) program, which will offer seed grants for work by Caltech and UCLA faculty members. The awards will support highly competitive applications proposing research that has the potential to move toward clinical applications. Each TAG will consist of an initial one-year award of up to $100,000 to support direct research costs, with the possibility of a one-year extension. Source: EurekAlert! 12/16/09

Researchers Initiate Phase II Trial of Stem Cells and Acute Heart Attack

The second phase of a clinical trial testing a new stem cell-based therapy on injured heart muscle has been launched by researchers at the University of Texas Medical School at Houston. Results from Phase I of the trial were published in December in the Journal of the American College of Cardiology. Researchers reported that patients were treated safely with intravenous adult human mesenchymal stem cells (Prochymal) after a heart attack. In addition, they had fewer arrhythmias, improved heart and lung function, and improvement in overall condition. "We are able to use a stem cell product that is on the shelf without prior preparation of anything from the patient, and this product appears to be able to help the heart muscle recover after a heart attack," said Ali E. Denktas, MD, the trial's Houston site principal investigator and assistant professor of cardiology. "This means patients have the potential to recover quicker with less risk of an immediate secondary attack." In many cell-based therapies, doctors harvest the patient's own cells, process them, and then return them to the patient. Prochymal, developed by Osiris Therapeutics, Inc., contains adult mesenchymal stem cells from healthy donors. The cells can be stored at an emergency center until needed. For purposes of the Phase II study, Prochymal must be administered within seven days of a heart attack. Neither patients nor their physicians know whether they received the stem cell drug. Adult mesenchymal stem cells appear to have anti-inflammatory, antifibrotic, and tissue regenerative capacities, as shown in both animal studies and human clinical trials, according to Osiris Therapeutics, Inc. Source: EurekAlert! 12/8/09

Medical School to Receive $19.7 Million to Study Tuberculosis Treatment Drugs

John L. Johnson, MD, professor of medicine at Case Western Reserve University (CWRU) School of Medicine and pulmonologist at University Hospitals Case Medical Center, has been awarded a 10-year, $19.7 million contract from the U.S. Centers for Disease Control and Prevention to lead an international clinical trials site for the Tuberculosis Trials Consortium (TBTC). TBTC, established in 1993, is a partnership of U.S. and international clinical investigators who conduct research about the diagnosis, medical treatment, and prevention of tuberculosis (TB) infection and disease. As the principal investigator, Johnson will lead two research teams in the testing of new drugs and shorter and simpler regimens for the treatment of TB that will benefit patients worldwide. The medical school will oversee international trial sites in Uganda and the Philippines. Roy Mugerwa, MBChB, MMed, will lead the TBTC site at the Uganda-CWRU Research Collaboration in Kampala, Uganda, globally, one of the most productive centers for TB research. The contract also supports the addition of a new trial site at the Tropical Disease Foundation in Makati City, Philippines, which will be under the direction of Thelma E. Tupasi, MD. The two sites will enroll patients for clinical trials and substudies conducted by the TBTC; participate in working groups, committees, and protocol teams of the consortium; and pursue other work to improve TB treatment for patients and TB control programs worldwide. Finally, Kathleen Eisenach, PhD, of the University of Arkansas for Medical Sciences, will provide microbiology consulting. Source: Newswise 12/8/09

Research Partnership is First to Test New Cancer Drug by Italian Firm

TGen Clinical Research Services at Scottsdale Healthcare (TCRS) is the world's first clinical trials site for a new drug designed to halt cancer cell division. NMS-1286937 is produced by Nerviano Medical Sciences of Milan, Italy's largest pharmaceutical research and development facility. NMS-1286937 is designed to stop cancer from spreading by preventing mitosis, the process of cell division. TCRS is a partnership between the Translational Genomics Research Institute (TGen) and Scottsdale Healthcare that enables laboratory discoveries to be quickly turned into targeted therapies that can be tested with patients at the Virginia G. Piper Cancer Center in Scottsdale. This Phase I clinical trial of as many as 40 adults with solid tumors will help determine if NMS-1286937 is safe and effective, and should lead to further clinical assessment. NMS-1286937 is a potent and selective polo-like kinase 1 inhibitor. High expression of polo-like kinase 1 is present in a wide range of cancers, including lung, colorectal, breast, pancreatic, head, neck, thyroid, and ovarian cancer. NMS-1286937 will be administered orally. Preclinical studies demonstrated that NMS-1286937 is effective against even aggressive cancers known to be resistant to the current standard of care. Source: EurekAlert! 12/8/09

Questioning the Validity of Cost-Effectiveness Models Based on Randomized Clinical Trials

Cost-effectiveness studies are widely used to guide prescribing policy in many countries, as part of health technology assessment programs. However, a new study published in December in PLoS Medicine by Tjeerd-Pieter van Staa and colleagues suggests that cost-effectiveness analyses based on data from randomized controlled trials may not be realistic enough to accurately inform policy. In the study, the researchers (affiliated with the General Practice Research Database in the U.K., the London School of Hygiene & Tropical Medicine, and Utrecht University in the Netherlands) specifically examine the relative cost-effectiveness of two commonly used groups of painkillers: selective cyclooxygenase-2 inhibitors (cox-2 inhibitors) versus conventional nonsteroidal anti-inflammatory drugs (NSAIDs). One type of cox-2 inhibitor has now been withdrawn from use, and recommendations regarding the use of others have changed as a result of data on cardiovascular harms associated with these drugs. The researchers collected data on the risk of upper gastrointestinal effects associated with use of either type of drug, and calculated the cost-effectiveness of the drugs in relation to these events using either data from large randomized controlled trials or from routine clinical practice--using the U.K. General Practice Research Database. These analyses showed that the average cost of preventing an upper gastrointestinal effect by switching NSAIDs for a cox-2 inhibitor was calculated at roughly $104,000 (U.S.) using the data from routine clinical practice. However, the cost effectiveness was calculated as around $20,000 using randomized trial data. Van Staa says: "Real-world questions on what to prescribe to whom should consider the varied group of patients in actual clinical practice, rather than just using data from highly selective randomized trials that have narrow inclusion criteria." Source: EurekAlert! 12/7/09

Healthcare Reform Lessons Found in New Book on Old Tuskegee Experiment

The Tuskegee Syphilis Study has become the American metaphor for medical racism, government malfeasance, and physician arrogance. The subject of histories, films, rumors, and political slogans, it received an official federal apology from President Bill Clinton in a White House ceremony attended by Wellesley College Professor Susan M. Reverby, one of those responsible for making the apology happen. In her new book, "Examining Tuskegee: The Infamous Syphilis Study and Its Legacy" (University of North Carolina Press, 2009), Reverby details the study’s racist history, explains how people experienced it, and why the doctors thought it was the right thing to do. Reverby overturns common myths and explores new lessons. Taking advantage of the recently opened medical records, hundreds of documents and scores of interviews, she reexamines the notorious federally sponsored medical experiment that targeted hundreds of poor rural African-American men with late-stage syphilis and ran unabated for decades. Reverby says the 40-year Tuskegee study has had a profound affect on the ethics and rules surrounding medical research and informed consent. One of the fictions about the study involves the persistent belief that the Public Health Service doctors who ran it actually infected the men with syphilis. Not true, Reverby points out. “Actually, they just watched and watched,” she said. “Yet the assumption that the men were injected with the disease continues to pass virally from one news source to another, from one person to another. It makes a better story and feeds our fears about experimentation. It builds on an acknowledgment of racism and makes these men into perfect victims. It links the Tuskegee story to other examples of moral failings in research.” Even today, those opposed to the H1N1 vaccine argue that Tuskegee should be our warning not to accept government care. “It is just the opposite,” Reverby contends. “The study should teach us about why the government needs to provide affordable care. If these men had decent heathcare, they would never have agreed to be in what they thought was a ‘treatment’ program. It is reminder of the need for informed consent and vigilance, not rejection, of medical science and the necessity for government help.” Source: Newswise 12/4/09

Cancer Study Takes Major Step Toward Improved Treatment

Cancer researchers at the University of Oklahoma Health Sciences Center have found a way to turn ineffective new cancer drugs into cancer-fighters. By using their patented chemical compound, SHetA2, researchers tricked cancer cells into responding to new treatments and undergoing cell suicide. The research appears in the journal Gynecologic Oncology. "This discovery means that we can use our nontoxic cancer prevention pill to improve treatment for people who already have cancer," said Doris Mangiaracina Benbrook, PhD, principal investigator on the project. "[The] studies to date have [found no] side effects of taking our drug, giving hope that we can prevent cancer in healthy people and improve treatment for cancer patients without increasing toxicity." The latest study looked at an upcoming class of cancer treatment drugs that worked well in experimental models, but proved ineffective against many human tumors. Benbrook and her team decided to test their compound's ability to "fix" the problem. It worked. "The new chemotherapy drugs are antibodies that bind to cell surface receptors called 'Death Receptors.' The binding of the antibodies activates the death receptors in cancer cells and causes cell suicide with little harm to normal cells. Many cancers, however, are resistant to the antibodies," Benbrook said. "We've shown that SHetA2 treatment can make ovarian and kidney cancer cells sensitive to the death receptor antibodies and kill the cancer." Benbrook said the compound will work with several cancers, including lung, kidney, ovarian, colon, and pancreatic cancer. Benbrook and her research team have patented the compound and hope to start clinical trials within a year. If the compound continues to be found safe, it would be developed into a pill to be taken daily like a multivitamin to prevent cancer. This new discovery means that the pill also could be used to make patients who already have cancer better respond to treatment. Source: EurekAlert! 12/1/09

Clinical Research Building Awarded Prestigious LEED Certification

The Clinical Research Building at the University of Miami Miller School of Medicine has been honored for its sustainability components. The building was awarded the LEED® designation, established by the U.S. Green Building Council and verified by the Green Building Certification Institute. LEED is the nation's preeminent program for the design, construction, and operation of green buildings. The building achieved LEED certification specifically for its energy, water, and material uses, and for incorporating a variety of other sustainable strategies. The 15-story, 336,000 square-foot building’s main purpose is to support the continued growth of the school’s clinical research programs and to consolidate current clinical research programs into a single facility. Source: EurekAlert! 12/1/09

Translational Medicine Program Awarded $700,000 Grant

The Graduate Training Program in Translational Medicine at the University of North Carolina (UNC) at Chapel Hill has been awarded a four-year, $700,000 "Med into Grad" renewal grant from the Howard Hughes Medical Institute. The initiative encourages graduate schools to integrate medical knowledge and an understanding of clinical practice into their biomedical doctoral programs. It is part of a long-term effort to increase the number of researchers who are able to turn basic science discoveries into improved treatments for patients. The UNC School of Medicine is one of 23 schools nationwide selected to receive up to $700,000 over four years to develop a program that brings clinical medicine into the graduate school curriculum. Source: EurekAlert! 11/30/09

Clinical Trials Launched for Treating Most Aggressive Brain Tumor with Personalized Cell Vaccines

The University of Navarra Hospital in Spain has launched a series of clinical trials in order to assess the efficacy of an immunotherapy treatment. This approach involves the application of personalized vaccines—produced from healthy and tumor cells from the patient him or herself—and designed to combat glioblastomas, one of the most aggressive and frequent malignant tumors. The new therapy is administered to participating patients combined with the standard, first-line treatment involving surgical extirpation of the tumor followed by radiotherapy and chemotherapy treatment with temozolomide. The hospital plans to involve a sample of 37 patients for the research. In essence, the production of the personalized vaccines is carried out at the hospital's Cell Therapy Good Manufacturing Practices Laboratory, where tumor proteins are processed and then combined with immune system cells obtained from the patient's blood, which are taught how to organize an immune response to the tumor. These prepared items are frozen and then administered to the patient as vaccines over the following months, in combination with conventional therapy. Source: EurekAlert! 11/30/09

Cancer Center Joins One of Nation's Largest Cancer Clinical Trials Groups

The Baylor Charles A. Sammons Cancer Center has become a full member of one of the largest cancer clinical trials cooperative groups in the United States. Funded by research grants from the National Cancer Institute, Southwest Oncology Group conducts clinical trials to prevent and treat cancer in adults, and to improve the quality of life for cancer survivors. "Joining this prestigious group will allow us to offer additional, important clinical trials to cancer patients in North Texas," said Alan M. Miller, MD, PhD, medical director of the center and chief of oncology for Baylor University Medical Center. "We are honored to work with our colleagues throughout the country and world in participating in clinical trials that are making great progress in the fight against cancer." Southwest Oncology Group has more than 5,000 affiliated physician researchers participating at 516 institutions in the United States, Canada, Puerto Rico, Sweden, and Saudi Arabia. The group conducts large Phase III trials, such as an ongoing prostate cancer prevention study with more than 35,000 men enrolled, as well as a newly opened trial in women with breast cancer to test the effectiveness of three drugs in preventing or delaying metastasis to the bone. Southwest Oncology Group also conducts groundbreaking Phase I and Phase II studies to test new targeted therapies and tissue studies that put to work the latest discoveries in cancer genetics. Source: PRNewswire 11/24/09

Foundation Backs Four Clinical Trials for New Parkinson's Interventions

The Michael J. Fox Foundation for Parkinson's Research in November announced awards totaling about $2.2 million to four research teams conducting new clinical research in Parkinson's disease. Two teams will undertake trials to address complications brought on by currently available treatments for Parkinson's disease. Anders Bjorklund, MD, PhD, of Lund University (Sweden), and colleagues have been funded by the foundation since 2005 to advance their hypothesis that the brain's serotonin system plays a role in dyskinesia, the excessive movements brought on by long-term dopamine replacement therapy. Now the team is initiating a pilot study of eltoprazine, a drug candidate capable of blocking inappropriate release of dopamine from serotonin terminals. The one-year pilot study will enroll 24 Parkinson's patients with dyskinesia at two sites in Sweden. If eltoprazine proves effective in alleviating dyskinesia, the pilot study could lead to a larger clinical trial. Meanwhile, Daniel Weintraub, MD, of the University of Pennsylvania, will conduct the first placebo-controlled trial of an agent to treat impulse control disorders associated with certain Parkinson's disease treatments known as dopamine agonists. Naltrexone, which blocks opioid receptors, is approved by the U.S. Food and Drug Administration for the treatment of alcohol dependence and has shown a benefit for pathological gambling; it has also been shown to be safe and well-tolerated in people with Parkinson's. In this three-year study, Weintraub will explore its safety and efficacy against impulse control disorders in 48 Parkinson's patients diagnosed with one or more impulse control disorders that developed in the context of dopamine agonist treatment. Two other teams will investigate nonpharmacological interventions with potential to address Parkinson's patients' unmet needs. Alvaro Pascual-Leone, MD, PhD, of Harvard Medical School, will test the potential of noninvasive repetitive transcranial magnetic stimulation to improve both motor and mood symptoms in Parkinson's disease. Daniel Tarsy, MD, of Harvard Medical School, will lead the SING-PD trial (Singing In Groups for Parkinson's Disease) to investigate whether group singing can improve the decreased voice volume experienced by many Parkinson's patients, which can lead to distress, social embarrassment, and social isolation. Source: PRNewswire 11/10/09

Hospital and Institute to Begin Proton Therapy Clinical Trial

St. Jude Children's Research Hospital and the University of Florida Proton Therapy Institute have formed a collaboration to provide proton therapy for St. Jude patients. The announcement follows the approval of the first clinical study to evaluate the use of proton therapy for rare brain cancers in children younger than 3 years old. Under the clinical protocol, St. Jude will refer patients to receive proton therapy at the institute in Jacksonville, Fla. The purpose of the clinical study is to improve response rates and decrease treatment-related side effects. Proton therapy is being studied as a way to reduce potential damage to healthy tissue that may result from conventional radiation therapy. This is especially important in treating children with brain and spinal tumors to potentially avoid interference with development, growth, and cognitive functioning. St. Jude patients accepted for the clinical study will be in Jacksonville for proton therapy treatment for six to eight weeks. It is expected that up to 15 patients will receive treatment during the first year of the study. Source: PRNewswire 11/9/09

Study Points to New Uses, Unexpected Side Effects of Existing Drugs

Scientists at the University of North Carolina (UNC) at Chapel Hill School of Medicine and the University of California, San Francisco (UCSF) have developed and experimentally tested a technique to predict new target diseases for existing drugs. The researchers developed a computational method that compares how similar the structures of all known drugs are to the naturally occurring binding partners--known as ligands--of disease targets within the cell. In a study published in Nature, the scientists showed that the method predicts potential new uses as well as unexpected side effects of approved drugs. "This approach uncovered interactions between drugs and targets that we never could have predicted simply by looking at the chemical structures," said senior study author Bryan Roth, MD, PhD, professor of pharmacology and director of the National Institute of Mental Health Psychoactive Drug Screening Program at UNC (pictured here). "We may now have a way to predict what side effects are likely to occur from treatment before we even put a drug into clinical testing." The discovery of surprising uses of developed drugs can sometimes be the result of serendipity, as unforeseen side effects emerge from clinical trials. In the past, researchers have tried to predict drug interactions by looking for chemical similarities among the possible targets of pharmaceutical compounds. However, some drug targets which look very similar to one another bind very different ligands, and some targets that don't have any obvious similarity bind similar ligands, says Brian Shoichet, PhD, co-senior study author and professor of pharmaceutical chemistry at UCSF. "So if instead we were to organize targets by the ligands they recognize, it could reveal different patterns than traditional approaches, and illuminate new opportunities for drugs to bind to unexpected targets." A team of researchers led by Roth and Shoichet did just that, comparing the structures of 3,365 Food and Drug Administration-approved and investigational drugs against the structures of hundreds of targets, defining each target by its ligands. They then honed in on 30 of the strongest predictions, validating the actual physical interactions between the drugs and targets in wet laboratory experiments. Roth says the power of their approach is it can be used to uncover the real targets of pharmaceutical compounds quickly and efficiently, and will probably lead to a greater understanding of the many molecular targets of each drug. "Drugs are not as selective as we once thought," said Roth. "It turns out that the most nonselective drugs are frequently the most effective for complex diseases. Rather than 'magic bullets,' we need to come up with 'magic shotguns' that hit more than one molecular target at a time. We could use this computational approach to identify the drugs that hit the right targets and miss the wrong ones." Funding for the studies at UNC and at UCSF came from the National Institutes of Health. Source: EurekAlert! 11/3/09

NIH-Supported Trial Focuses on Testosterone Therapy in Older Men

Penn Medicine will lead a new national $45 million clinical trial to test whether testosterone therapy can favorably affect certain conditions affecting older men. Low serum testosterone may contribute to a number of problems affecting older men, including decreased ability to walk, loss of muscle mass and strength, decreased vitality, decreased sexual function, impaired cognition, cardiovascular disease, and anemia. While testosterone normally decreases with age, in some men, low levels of testosterone may contribute to these debilitating conditions. Led by the University of Pennsylvania School of Medicine and conducted at 12 sites across the nation, the Testosterone Trial will involve 800 men age 65 and older with low testosterone levels. The National Institute on Aging, part of the National Institutes of Health (NIH), is providing support for the trial, which will include five separate studies. At each of the 12 sites, men 65 and older with low serum testosterone and at least one of the following conditions—anemia, decreased physical function, low vitality, impaired cognition, or reduced sexual function—will be randomly assigned to participate in a treatment group or a control group. Treatment groups will be given a testosterone gel that is applied to the torso, abdomen, or upper arms; control groups will receive a placebo gel. Serum testosterone will be measured monthly for the first three months and quarterly thereafter up to one year. Participants will be tested on a wide range of measures to evaluate physical function, vitality, cognition, cardiovascular disease, and sexual function. Recruitment of study participants began in October. Participating institutions include University of California, Los Angeles; University of California, San Diego; Boston University, Mass.; University of Pittsburgh, Pa.; Albert Einstein College of Medicine, Bronx, N.Y.; Baylor College of Medicine, Houston, Texas; University of Minnesota, Minneapolis; Yale University, New Haven, Conn.; University of Alabama at Birmingham; University of Washington, Seattle; Northwestern University, Evanston, Ill.; and University of Florida, Gainesville. Solvay Pharmaceuticals is also supplying the study drug. Source: EurekAlert! 11/2/09

Digital "Plaster" for Monitoring Vital Signs Undergoes First Clinical Trial

A wireless digital "plaster" that can monitor vital signs continuously and remotely is being tried out in a new clinical trial with patients and healthy volunteers at the Imperial College Healthcare National Health Service Trust in the United Kingdom. Toumaz Technology Ltd's Sensium™ digital plaster (or patch) is a disposable device that sticks to a patient's chest. It is designed to allow patients to have their health monitored continuously without being wired up to bulky, fixed monitoring machines, potentially freeing some patients from their hospital beds. The digital plaster is based on innovative technology created by engineers at Imperial College London. It contains a wireless, smart, ultra-low power sensor platform in a silicon chip, which can monitor a range of vital signs, including body temperature, heart rate, and respiration, in real-time. The intention is that healthcare professionals will be able to download this information using a mobile phone, enabling them to pick up on any critical changes in their patients' status on a round-the-clock basis and allowing early detection and treatment of any unforeseen complications. The data can also be integrated automatically into the patient's electronic medical record. The team that developed the plaster hopes that it will enable some patients to recover from surgery and illness at home rather than in hospital. It should also mean that hospital in-patients have greater mobility. In addition, it could allow doctors to extend continuous monitoring of vital signs to a broader range of patients. The disposable plaster has a working life of several days, after which it can be replaced, ensuring that infection control can be maintained. In the new trial, which is funded by CareFusion, researchers will explore whether the physiological data that doctors and nurses can obtain using the digital plaster system is equivalent to that which can be acquired using the current gold-standard monitors in use in hospitals. Source: EurekAlert! 11/2/09

Multicenter Study Finds Early Results of Therapy for Preemies Not Sustained

Inhaled nitric oxide (iNO), a therapy used in the treatment of premature newborns with respiratory failure that had shown promising results in short-term studies, does not significantly improve long-term outcomes, according to a national study led by critical care researchers at the University of Pittsburgh School of Medicine and the Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center. Previous studies of iNO in premature babies with respiratory failure suggested improvements in early outcomes, but this study of nearly 800 infants found no significant improvement in survival rates at one year of age and no change in longer term respiratory or neurological function. Further study will determine if a different dose, longer duration of therapy, and/or use in a different subgroup of premature babies would be effective. Results of the study are published in the November issue of Pediatrics. Researchers conducted long-term follow-up of premature newborns from 16 centers in the United States who were born at 34 weeks or earlier and weighed between 500 and 1,250 grams and were enrolled in a study testing whether iNO could prevent chronic lung disease. Babies received five parts per million of iNO or a placebo within the first two days of birth and continuing for 21 days (or until the patient was taken off a ventilator). Of the 590 babies with complete survival data, 77 percent survived to one year of age (79 percent of those receiving iNO and 75 percent of those receiving placebo). At one year of age, less than 6 percent of study participants were still receiving supplemental oxygen, but most had continued neurologic impairment. Less than 38 percent of survivors were unimpaired and nearly 35 percent had severe neurologic impairment. In all, nearly 45 percent of patients from the study had died, were on oxygen, or had neurologic impairment, and there were no significant differences between those who had received iNO and those who had received placebo. The study was funded by the National Institutes of Health and Ikaria. Source: EurekAlert! 11/2/09

Progress Made on Group B Streptococcus Vaccine

Scientists supported by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, have completed a Phase II clinical study that indicates a vaccine to prevent Group B Streptococcus (GBS) infection is possible. GBS is the most common cause of sepsis and meningitis in newborns in the United States. It can also cause severe illness in pregnant women, the elderly, and adults with chronic illnesses. Colonization of the genital or gastrointestinal tract is a critical risk factor for infections due to GBS. The researchers, led by Sharon L. Hillier, PhD, from the Magee-Womens Research Institute at the University of the Pittsburgh, found that the vaccine used in the study can cause a modest, but sustained reduction in genital and gastrointestinal GBS bacterial colonization. The GBS bacterium, which is commonly found in the gut and genital tracts, can infect the fetus during gestation and birth or after delivery. Pregnancy-related infections can lead to serious consequences for women including stillbirth. Currently, one-third of pregnant women in the United States test positive for asymptomatic GBS and receive antibiotics during labor to prevent infection of the newborn. Although this antibiotic strategy is highly effective, the broad use of antibiotics in pregnant women is of concern to public health officials. Many women are allergic to penicillin and penicillin-type antibiotics that are the preferred treatment, and GBS is increasingly resistant to other common antibiotics. Hillier and her colleagues conducted a double-blind, randomized trial of the GBS vaccine that included a total of 650 sexually active, nonpregnant women ages 18 to 40 who were GBS-negative in the vagina and rectum at the beginning of the study. Approximately one-half of the women were in the control group and received a licensed tetanus and diphtheria toxoids vaccine instead of the GBS vaccine. The women were followed for 18 months after they were vaccinated and checked for GBS bacteria at regular intervals. The goal of the study was to see whether vaccination could prevent or decrease colonization by one of the most common subtypes of GBS bacteria: Type III. Although the vaccine had a modest effect on bacterial colonization (36 percent in the vagina and 43 percent in the rectum), it provided some protection over the entire period of the study. The GBS vaccine also was found to be safe and well-tolerated, and elicited a strong immune response. The next step to prevent GBS disease would be to develop vaccines that provide protection against a broader range of GBS types and test them in clinical trials. Source: EurekAlert! 10/30/09

Grants to Drive Development of Stem Cell Therapies for Diabetes, Brain Tumors

Two teams of University of California, San Francisco (UCSF) scientists have received grants from the California Institute for Regenerative Medicine (CIRM) to advance their stem cell based strategies for treating diabetes and brain tumors. The intent of the grants is for teams to file new drug applications to the U.S. Food and Drug Administration (FDA) within four years, driving potential therapies toward clinical trials. The two grants, awarded to collaborative scientific teams, total $39.2 million. The projects are among 14 disease team grants announced in late October by CIRM. The grants focus on conditions ranging from brain tumors and diabetes to HIV, heart damage, and amyotrophic lateral sclerosis, among others. They are the first issued by CIRM with the explicit intent of driving the development of therapies for approval by FDA for testing in clinical trials. The multidisciplinary collaborations are intended to hasten the clinical trial development process, avoiding mistakes sometimes discovered late in the game and ensuring that clinically relevant issues are considered early. The goal of the diabetes team is to encapsulate islet progenitor cells generated from human embryonic stem cells in a durable, retrievable device and implant them into patients. The cells, which differentiate into glucose responsive islet beta cells after transplantation in vivo, have proven to be a successful strategy in treating rodents with chemically-induced diabetes. If the preclinical work is successful, a Phase I safety trial in Type 1 diabetic patients could begin within three to four years of the initiation of the project. The goal of the brain tumor team is to refine its strategy of using adult and fetal neural stem cells, as well as mesenchymal stem cells, genetically engineered to contain a tumor-killing gene to home in on glioblastoma multiforme, the most common and aggressive form of brain tumor. The studies in rodents engineered to develop human brain tumors were successful. If the strategy is approved by the FDA, it would be tested first in patients with recurring glioblastoma multiforme. Source: EurekAlert! 10/29/09

Researchers Find Room Design Can Enhance Patient Care

The design of a consultation room can improve the quality of a visit to the physician's office. A collaborative research study developed by Nurture (the healthcare division of Steelcase) and Mayo Clinic was conducted to understand the extent to which a consultation room designed to support present-day clinical encounters could affect the consultation between patients and clinicians. The results of this randomized trial, the first of its kind, appear in the October issue of Health Environments Research and Design Journal. "This study supports the notion that the space in which people meet can influence how they work together," says Victor Montori, MD, the lead Mayo researcher. He also says more studies in other healthcare systems are needed to confirm these findings. You can view him discussing the study on YouTube here. The Space and Interaction Trial consisted of 63 pairs of patients and doctors. The pairs were assigned by chance to either a conventional office or to an experimental one. The experimental office placed the patient and the clinician side by side facing the computer screen while seated at a semicircular desk. The researchers found that patient and clinician satisfaction with the conventional office was very high. In the experimental room, however, researchers determined that clinicians could share more information with patients while both viewed the computer screen. They also noted that patients felt they had more and better access to information, including their own records, test results, images, and online patient education material. These findings are the result of a postvisit follow-up survey with the participants. The study took place during usual patient visits at Mayo Clinic, and was funded by Steelcase. Source: EurekAlert! 10/28/09

Neuroscientist's Discovery of New Uses for Old Drug Leads to Patents, Award

University of South Florida neuroscientist R. Douglas Shytle's discovery of successful new clinical uses for mecamylamine, a drug once used to treat hypertension, has led to several issued patents on mecamylamine and related compounds. In October, Shytle, associate professor and research scientist at the university's Center of Excellence for Aging and Brain Repair and the Silver Child Development Center, received the university's 2009 "Excellence in Innovation" award. The award recognizes Shytle's translational research achievements in developing new intellectual property based on clinical research and novel pharmacological discoveries which have led to newly commercialized therapeutics. His most recent success is with a new experimental antidepressant, known as TC-5214, which is covered by university patents and licensed to Targacept, Inc., a clinical-stage biopharmaceutical company that develops neuronal nicotinic receptor therapeutics. Targacept recently announced the positive results on TC-5214 as add-on treatment in a large clinical trial of adult patients with treatment-resistant major depressive disorder. TC-5214 is a unique form of Merck's mecamylamine, once used to treat severe hypertension in the 1950s. Because later research suggested that mecamylamine interacted with brain nicotine receptors, Shytle and others thought it might have a variety of therapeutic effects similar to nicotine, but without the side effects and addiction. Building on earlier clinical research using transdermal nicotine to treat patients with Tourette's syndrome (characterized by body movements [tics] and vocalizations), Shytle worked closely with other university researchers to investigate the effects of mecamylamine in Tourette's patients to see if it could help control their symptoms, as observed with nicotine. "After carefully designing and conducting a large clinical trial in children with Tourette's syndrome in 1999, we were shocked and disappointed to find that the drug had no effect on the tic symptoms," Shytle said. "After reading several reports about how many antidepressants appeared to be interacting with nicotine receptors the same way as mecamylamine did, we decided to go back and take a second look at the data from our clinical trial. And there it was, like finding a gold nugget buried under the sand, clear evidence for an antidepressant effect of mecamylamine, but not for the placebo, in those Tourette's subjects who had depressive symptoms." Based on those clinical findings, the researchers published a hypothesis paper in the prestigious journal, Molecular Psychiatry, proposing that nicotine receptor blockade might represent a novel pharmacological target for achieving therapeutic antidepressant properties. That hypothesis has now been supported by three clinical trials with mecamylamine, one by a group at Yale and two larger studies conducted by Targacept. The latest trial was conducted using TC-5214, predicted by the university patents to be more effective with fewer side effects when compared to the older parent drug. Source: EurekAlert! 10/27/09

Trial Raises Doubts Over Alternative Pain Therapy for Arthritis

Copper bracelets and magnetic wrist straps are ineffective in relieving arthritis pain, according to a new study led by a University of York academic. U.K. researchers conducted the first randomized, placebo-controlled trial on the use of both copper bracelets and magnetic wrist straps for pain management in osteoarthritis--the most common form of the condition. The devices are used worldwide for helping to manage pain associated with chronic musculoskeletal disorders. The results of this trial conflict with those from previous studies, by showing that both magnetic and copper bracelets were ineffective for managing pain, stiffness, and physical function in osteoarthritis. The research is published in the latest issue of the journal Complementary Therapies in Medicine. According to trial leader Stewart Richmond, a Research Fellow in the university's Department of Health Sciences, "It appears that any perceived benefit obtained from wearing a magnetic or copper bracelet can be attributed to psychological placebo effects. People tend to buy them when they are in a lot of pain, then when the pain eases off over time, they attribute this to the device. However, our findings suggest that such devices have no real advantage over placebo wrist straps that are not magnetic and do not contain copper." The trial involved 45 people aged 50 or more, who were all diagnosed as suffering from osteoarthritis. Each participant wore four devices in a random order over a 16-week period--two wrist straps with differing levels of magnetism, a demagnetized wrist strap, and a copper bracelet. The study revealed no meaningful difference between the devices in terms of their effects on pain, stiffness, and physical function. The trial also involved researchers from the University of Hull and University of Durham, and from the National Health Service. Source: EurekAlert! 10/16/09

Grant Funds Comparative Effectiveness Research

A $4 million National Cancer Institute (NCI) grant will help position the Southwest Oncology Group, one of the largest NCI-funded clinical trial cooperative groups, as a national leader in comparative effectiveness research on cancer. The Grand Opportunities award supports the development of the Center for Comparative Effectiveness Research in Cancer Genomics (CANCERGEN) under the direction of Scott Ramsey, MD, PhD, of the Fred Hutchinson Cancer Research Center in Seattle, Wash. Researchers at the University of Washington in Seattle and the Center for Medical Technology Policy in Baltimore, Md. will co-lead the effort. CANCERGEN will create a comprehensive process to evaluate emerging cancer genomics technologies and identify those that are most promising. The University of Michigan-based Southwest Oncology Group will use this process to help it select and launch those clinical trials that will have the greatest impact. The first trial proposal slated for support under CANCERGEN will assess whether a genetic test known as the Oncotype DX assay can predict which patients with node-positive breast cancer will benefit from chemotherapy and which patients will not. The genetic assay is expensive, costing about $3,500 per test, yet the chemotherapy treatment now routinely given to node-positive breast cancer patients costs on the order of $50,000 per year. If the Oncotype DX assay does prove to predict which node-positive patients will see no benefit from this chemotherapy, it could spare thousands of women the grisly effects of a course of chemotherapy that will not help lengthen their life, while at the same time saving hundreds of millions of dollars in healthcare costs each year. Source: EurekAlert! 10/15/09

University to Continue Work in NIH's Rare Diseases Clinical Research Network

The University of North Carolina (UNC) at Chapel Hill has been awarded a five-year, $6.2 million renewal grant to continue its work as part of the National Institutes of Health's (NIH's) Rare Diseases Clinical Research Network (RDCRN). Within the RDCRN, UNC is the lead institution in a study of rare genetic airways disorders, such as cystic fibrosis and primary ciliary dyskinesia. UNC also heads a multicenter group within the network, called the Genetic Diseases of Mucociliary Clearance Consortium. Other institutions in the consortium reporting to UNC include Washington University in St. Louis, Mo., the Children's Hospital in Denver, Colo., Children's Hospital & Regional Medical Center in Seattle, Wash., the National Institute of Allergy and Infectious Diseases, Lucille Packer Children's Hospital at Stanford University, and the Hospital for Sick Children in Toronto. Since its creation in 2003, the RDCRN has enrolled more than 5,000 patients in 37 clinical studies in rare diseases. Patient recruitment for clinical studies is a fundamental challenge in rare diseases research, because there are typically so few affected patients in any one area. The RDCRN was designed to address this problem by fostering collaboration among scientists and shared access to geographically distributed research resources. Network consortia have also established training programs for clinical investigators who are interested in rare diseases research. Source: EurekAlert! 10/13/09

Cancer Drug Equal to Gold Standard Treatment for Macular Degeneration

Investigators from Boston University School of Medicine and the VA Boston Healthcare System have shown, at six months in a small group of patients, that there is no difference in efficacy between bevacizumab (Avastin) and ranibizumab (Lucentis) for the treatment of age-related macular degeneration (AMD). The study, which appears currently online in the American Journal of Ophthalmology, is the first to report early outcomes of a prospective, double-masked, randomized, controlled trial comparing the two Genentech drugs for the treatment of wet age-related macular degeneration. AMD is the leading cause of blindness over the age of 50 in developed Western countries. It can present in two forms, exudative (wet) or nonexudative (dry). The gold standard of treatment is ranibizumab, which was approved by the Food and Drug Administration (FDA) for AMD in 2006. Bevacizumab was FDA-approved for colorectal cancer in 2004, and has since been used worldwide as an off-label, local intravitreal treatment for wet AMD. Both have shown to be efficacious in the treatment of AMD, however, it is unknown which one is more effective. With a total of 20 subjects and a 2:1 randomization, early results of this trial suggest that visual outcomes of bevacizumab appear to be no different from ranibizumab. Head-to-head research of the two drugs continues as the National Eye Institute is sponsoring the Comparison of AMD Treatment Trials Study in 44 clinical centers throughout the United States. Early results are expected in 2011. Source: EurekAlert! 10/9/09

Michigan Hospital Launches Gene Therapy Study for Parkinson's Disease

A Michigan hospital is embarking on a research study for advanced Parkinson's disease using a state-of-the-art treatment called gene transfer. The clinical trial will test whether gene transfer therapy is able to restore better mobility in Parkinson's patients who have lost responsiveness to drug therapy. "The start of this clinical trial provides hope to a Parkinson's disease patient population that has had a long-standing need for better treatment options," says Henry Ford West Bloomfield Hospital neurologist Peter LeWitt, MD. Of the eight sites in the United States involved in the study, the hospital, part of the Henry Ford Health System, is the only Michigan institution testing this experimental therapy. Most current therapies and research approaches target dopamine to treat motor symptoms associated with Parkinson's disease. In contrast, the focus of the current gene therapy strategy is on increasing GABA, a brain neurotransmitter that regulates movement. In Parkinson's disease, GABA is reduced in an area of the brain called the subthalamic nucleus, causing it to be overactive. Investigators feel this might be a better way to help advanced Parkinson's disease. For the clinical trial, the gene therapy product rAAV-GAD will be placed into the subthalamic nucleus by a surgical procedure. The gene transfer is done through a catheter that is removed shortly after its placement. Participants will be assessed post-treatment at multiple intervals. As an alternative to this experimental treatment, patients with advanced Parkinson's disease have the option of deep brain stimulation. This also involves a surgical procedure in which a pacemaker-like device is placed in the brain to help in control of Parkinson's disease symptoms. Source: EurekAlert! 10/6/09

Cardiac Stem Cell Trial Seeks to Treat Some Heart Attack Patients

Researchers at University of California, San Francisco (UCSF) Medical Center have begun enrollment for an early-stage clinical trial to evaluate the safety and efficacy of an adult stem cell therapy for patients who have just experienced their first acute myocardial infarction, or heart attack. The trial is part of a multicenter national study. The cells used, known as mesenchymal stem cells, were obtained from the bone marrow of healthy adult donors. Depending on their location in the body, mesenchymal stem cells give rise to bone, cartilage, fat, muscle and connective tissue. The experimental therapy is intended to combat the symptoms related to heart damage that continue to develop following a heart attack, including low pumping capacity, inflammation and increased scar tissue. Although the exact mechanisms of the stem cells' actions in this setting are not yet known, previous studies have suggested that they could reduce the amount of scar tissue and inflammation caused by heart attack. The new clinical trial is the first stem cell clinical trial in cardiology at UCSF. All patients arriving at UCSF's Emergency Department with heart attack will continue to be treated with standard measures. Patients who meet the medical criteria for the trial will be able to elect to receive the stem cell therapy within seven days after their heart attack. The stem cell therapy is delivered to patients via a one-time IV infusion, performed onsite at UCSF. The infusion takes approximately half an hour. Patients will be followed for two years and progress will be assessed with MRI and ultrasound imaging in addition to the standard battery of cardiac measures, including electrocardiogram and heart function monitoring. The goal of the therapy is to prevent the permanent damage that heart attacks cause. The two-year Phase II trial will test the safety and efficacy of a stem cell therapy called Prochymal, developed by Osiris Therapeutics, Inc. Results from a Phase I trial that did not involve UCSF were announced by the company in February 2009. Source: EurekAlert! 10/6/09

Researchers Examine Use of Toad Venom in Cancer Treatment

Huachansu, a Chinese medicine that comes from the dried venom secreted by the skin glands of toads, has tolerable toxicity levels, even at doses eight times those normally administered, and may slow disease progression in some cancer patients, say researchers from the University of Texas M. D. Anderson Cancer Center. The results from the Phase I clinical study, a collaborative research project between M. D. Anderson and Fudan University Cancer Hospital in Shanghai, are reported online in the journal Cancer. The study marks the first time a formal clinical trial has examined the relationship between huachansu dose and toxicity, although the drug is common in China and approved by the Chinese Food and Drug Administration. Huachansu is widely used to treat patients with liver, lung, colon, and pancreatic cancer at oncology clinics in China. Chinese clinical trials conducted since the 1970s have demonstrated the anticancer properties of huachansu, citing total response rates of 10 percent and 16 percent observed in patients with advanced hepatocellular carcinoma and lung cancer, respectively. The clinical trial was conducted at the hospital in China with M. D. Anderson providing training and ongoing consultation. The institutions collaboratively designed the trial that was approved by both institutional review boards. M. D. Anderson and the hospital signed a sister institution agreement in 2003, creating a framework for research, educational, and clinical collaboration. A Phase II clinical trial comparing the effects of huachansu combined with gemcitabine (Gemzar®) to gemcitabine and placebo for patients with advanced pancreatic cancer is under way at the hospital in collaboration with M. D. Anderson. Both trials are part of the International Center of Traditional Chinese Medicine for Cancer funded by the National Cancer Institute. Anhui Jinchan Biochemistry Company, Ltd. provided the drug for this trial. Source: Newswise 9/24/09

Multicenter Study Finds Evidence Drug Might Slow Parkinson's

Following one of the largest studies ever conducted in Parkinson's disease (PD), researchers at Mount Sinai School of Medicine reported in the New England Journal of Medicine that rasagiline, a drug currently used to treat the symptoms of PD, may also slow the rate of disease progression. Known as ADAGIO (Attenuation of Disease Progression with Azilect Given Once Daily), the 18-month study used a novel design called the delayed start. In this type of study, patients are randomized to start active treatment early or late, and then researchers look to see if early treatment influences the outcome at final visit when patients in both groups are on the same treatment. ADAGIO showed that previously untreated PD patients randomized to initiate therapy with rasagiline (Teva Pharmaceuticals' Azilect®) 1 mg per day had benefits at 18 months that were not achieved when the same drug was initiated at nine months. These results are consistent with the possibility that the drug has a disease-modifying effect which slows disease progression. The study examined both 1 mg and 2 mg doses of rasagiline using a rigorous design that included three primary endpoints. The 1 mg dose met all three primary endpoints, but the 2 mg dose did not. If the results can be confirmed, rasagiline would be the first drug determined to have a disease-modifying effect in PD. The first PD trial to use delayed start as its primary design, ADAGIO was one of the largest trials ever conducted in this disease and included 1,176 patients with very early PD in 14 countries and 129 medical centers. They were randomized to receive rasagiline 1 or 2 mg per day for 72 weeks (early start) or placebo for 36 weeks followed by rasagiline 1 or 2 mg per day for 36 weeks (delayed start). Source: EurekAlert! 9/23/09

Historic Gene Therapy Trial to Treat Alzheimer's Disease Under Way

Researchers in the Memory Disorders Program at Georgetown University Medical Center are now recruiting volunteers for a national gene therapy trial--the first study of its kind for the treatment of patients with dementia due to Alzheimer's disease. The double-blind Phase II study examines the safety and possible benefits of CERE-110. CERE-110 contains a gene and is injected during surgery into a part of the brain affected by Alzheimer's disease. The gene will instruct brain cells to produce more of a protein, called Nerve Growth Factor (NGF), which helps nerve cells survive and function properly. About 50 people with Alzheimer's disease will participate in this study at fewer than 10 hospitals nationwide. Only persons with a mild form of Alzheimer's disease, who are evaluated and deemed competent to consent for themselves, will be permitted to participate in the study. The study requires each patient to select a study partner for the length of the study. All patients in the study will undergo surgery to drill two small holes in the skull. Only those patients randomly assigned to receive CERE-110 will have the gene therapy injected into the brain. Those subjects randomized to the placebo group will not have the gene therapy injected. This study is sponsored by the Alzheimer's Disease Cooperative Study (ADCS) through a grant from the National Institute on Aging (a part of the National Institutes of Health) in association with Ceregene, Inc, which will provide the active agent used in this study. Source: EurekAlert! 9/22/09

Foundation Announces Funding of First Clinical Trial with Disease-Modifying Therapy for Rett Syndrome

In September, the International Rett Syndrome Foundation announced that it will provide $200,000 in 2009 to support a newly proposed clinical trial with a growth factor-based treatment for Rett syndrome. The study will be carried out by a team of clinical trials specialists at the Boston Children's Hospital, led by Dr. Omar Khwaja MD, PhD, and will be the first potentially disease-modifying therapy ever to be tested in Rett syndrome patients. Investigators will test a drug called Increlex, an engineered form of the human protein Insulin-like Growth Factor-1, a Food and Drug Administration-approved drug for children with short stature due to severe Primary IGF-1 deficiency. Preliminary evidence in animal models of Rett syndrome has recently suggested that targeting the IGF-1 signaling axis may provide a potential avenue for therapy. Increlex will be provided gratis by Tercica Inc., a subsidiary of the IPSEN Group, which has reviewed and approved the trial through its internal scientific review board. Khwaja and his team have secured additional funding for this clinical trial through a grant provided by Harvard University's Catalyst Pilot Awards for Clinical Translational Research. Rett syndrome is a brain disorder affecting development in childhood that has been identified almost exclusively in females; it results in severe movement and communication problems following apparently normal development for the first six months of life. Source: EurekAlert! 9/21/09

New Program in International Research Ethics Commences

Students seeking a master's degree in philosophy at Indiana University-Purdue University Indianapolis (IUPUI) can select a new offering that will expose them to the growing field of international research ethics. A "Concentration in International Research Ethics" will be offered by the Department of Philosophy in the Indiana University School of Liberal Arts at IUPUI and the Indiana University Center for Bioethics. The new program was funded by a $940,000 grant the Center for Bioethics received from Fogarty International Center at the National Institutes of Health. The curriculum involves a mix of coursework and an innovative practicum experience in Kenya, where a parallel master's degree program is being developed at Moi University to integrate with the IUPUI program. The new program is designed to be completed in four semesters of full-time study, but part-time students are welcome to apply. A website will soon be available with details regarding curriculum structure, course descriptions, program faculty, and admission requirements. Source: EurekAlert! 9/18/09

Medications Effective in Reducing Risks for Breast Cancer Can Also Cause Serious Side Effects

Three drugs that reduce a woman's chance of getting breast cancer also have been shown to cause adverse effects, according to a new report from the Agency for Healthcare Research and Quality (AHRQ) in the U.S. Department of Health and Human Services. The report is based on a study led by Heidi D. Nelson, MD, MPH, research professor in the Oregon Evidence-Based Practice Center at Oregon Health & Science University and medical director of the Women and Children's Program and Research Center at Providence Health & Services. It is published online in the September 15 issue of the Annals of Internal Medicine. The study is the first to make a direct, comprehensive comparison of drugs that reduce the risk of breast cancer so that women and their healthcare providers can assess their potential effectiveness and adverse effects. It compares the use of tamoxifen, raloxifene, and tibolone to reduce the risks of getting breast cancer in women without pre-existing cancer. Tamoxifen, raloxifene, and tibolone can be prescribed to women with a family history of breast cancer or other risk factors, but prescribing practices vary widely. According to the study, all three drugs significantly reduce invasive breast cancer in midlife and older women, but benefits and adverse effects can vary depending on the drug and the patient. The most common side effects for tamoxifen are flushing and other vasomotor symptoms (e.g., night sweats, hot flashes), vaginal discharge, and other vaginal symptoms, such as itching or dryness; for raloxifene, side effects include vasomotor symptoms and leg cramps; and for tibolone, side effects include vaginal bleeding. The study also found that each drug carried risks of adverse effects. Tamoxifen increases risks of endometrial cancer, hysterectomies, and cataracts compared to the other drugs. Tamoxifen and raloxifene increase risk of blood clots, although tamoxifen's risk is greater. Tibolone carries an increased risk of stroke, according to the study. The study also examined the drugs' effectiveness and harms based on age, menopausal status, estrogen use, and family history of breast cancer, and sought to identify the kinds of women who might be good candidates for therapy, although the evidence is limited in this area. The investigators called for more research to more clearly identify characteristics of patients who would benefit from these drugs while suffering the least harm. Source: EurekAlert! 9/18/09

National Trial Testing New Treatment for Chronic, Severe Indigestion

Could medicines used for depression also treat chronic, severe indigestion? Scientists at Mayo Clinic suspect they can and, backed by funding from the National Institutes of Health (NIH), they are testing that premise in a nationwide clinical trial. "Nerve cells are found throughout the body, and just as their dysfunction in the brain can cause depression, we suspect overly sensitive nerves in the gut can produce this very uncomfortable indigestion," says Nicholas Talley, MD, PhD, chair of the trial and chair of the Department of Internal Medicine at the Mayo Clinic campus in Florida. The study, which will include 400 adult men and women who have been diagnosed with functional dyspepsia, is being offered at all three Mayo Clinic campuses (Florida, Minnesota, and Arizona) and at Northwestern University, Saint Louis University School of Medicine, Dartmouth-Hitchcock Medical Center, and Baylor College of Medicine. Trial participants will be treated for three months with one of two different types of Food and Drug Administration-approved antidepressant medications or with an inert placebo pill. The NIH recently expanded the trial's scope to include four times as many patients (more than 100 patients are in the study now), run for three more years, and receive an additional $1.2 million in federal support. The trial is based on findings from small studies using amitriptyline (Elavil) and escitalopram (Lexapro) that suggested abdominal pain may get better in adults with the disorder, says Talley. "We were excited by these early findings, which has led to this clinical trial," he says. "If it turns out that these drugs correct stomach emptying, stomach retention, and overall motility, we could help improve the quality of health and life for the millions of people with functional dyspepsia." Source: EurekAlert! 9/17/09

Partners Unveil Initiative to Launch Biomedical Research Program in the Middle East

The Qatar Foundation for Education, Science, and Community Development and the Weill Cornell Medical College in Qatar (WCMC-Q) have unveiled a major initiative to establish a world-class biomedical research program, the first of its kind in the Middle East. The program aims to form a biomedical research infrastructure, developing a scientific and technical workforce for the benefit of the region at large. Central to this endeavor is a partnership approach, bringing together institutions that have overlapping missions in medical education, research, and healthcare. The program will also support high quality research in the fields of genetic and molecular medicine, women's and children's health, gene therapy, stem cells, and vaccine development. Specific objectives include the development of first-rate translational and clinical research projects that will establish Qatar as a center of excellence with a focus on improving the health of the population, and the development of the biomedical research infrastructure encompassing laboratories and compliance and regulatory functions. WCMC-Q is part of the Weill Medical College of Cornell University, the first American institution to offer its medical degree overseas. Source: EurekAlert! 9/15/09

Extremity Trauma Clinical Research Consortium to be Established

The Johns Hopkins Bloomberg School of Public Health has been awarded $18.4 million by the Orthopaedic Extremity Trauma Research Program of the U.S. Department of Defense to establish an Extremity Trauma Clinical Research Consortium. The Bloomberg School will serve as the coordinating center for the consortium, which will include a network of 12 core civilian trauma centers working together with several major military treatment centers and the U.S. Army Institute of Surgical Research at Fort Sam Houston, Texas. The overarching goal of the consortium is to conduct multicenter clinical research studies relevant to the treatment and outcomes of severe orthopaedic trauma sustained on the battlefield. These studies will help establish treatment guidelines and facilitate the translation of new and emerging technologies into clinical practice. "The need for such a consortium is evident," said Ellen MacKenzie, PhD, principal investigator and the Fred and Julie Soper Professor and Chair of the Bloomberg School's Department of Health Policy and Management. "Eighty-two percent of all service members injured in Operation Iraqi Freedom and Operation Enduring Freedom sustain extremity trauma. Many sustain injuries to multiple limbs. The research to be conducted by the Consortium will help us better understand what works and what doesn't in treating these injuries and ensure that our service members are provided with the best care possible." An important feature of the consortium will be its ability to expand the number of clinical sites participating in any one clinical study. More than 30 trauma centers around the country have pledged support for the consortium, and are eager to participate in one or more of the studies sponsored under its umbrella. The 12 core clinical centers participating in the consortium include Boston University Medical Center, the Florida Orthopaedic Institute, Carolinas Medical Center, Denver Health and Hospital Authority, OrthoIndy and the Indiana Orthopaedic Hospital, Orthopaedic Associates of Michigan, the Orthopaedic Trauma Institute at the University of California at San Francisco, San Francisco General Hospital, the University of Maryland Medical Center's R Adams Cowley Shock Trauma Center, the University of Mississippi Medical Center, the University of Texas Southwestern Medical Center, the University of Washington Harborview Medical Center and Vanderbilt University Medical Center. Source: EurekAlert! 9/11/09

Study Rejects Cancer Safety Fears of Common Heartburn Treatment

Fears about the cancer-causing effects of the second most prescribed group of drugs in the Western world have been put to rest, following the largest ever study into their use. "Proton pump inhibitors" (PPIs) are the most commonly used treatment for chronic acid reflux (heartburn). Despite their excellent safety record, it was unclear if long-term use of PPIs to reduce the discomfort of heartburn could increase the risk of developing either Barrett's Oesophagus (BE) or the spread of the associated cancer. New research carried out at Queen Mary, University of London and Leicester Royal Infirmary, has given the most conclusive evidence yet that this is not the case. The work is published in the peer reviewed journal Gut. Tests carried out during the two-year study looked at tissue sampled from the oesophagus lining of 90 volunteers, each of whom were given PPI drugs at either a high or low dosage. Researchers found there was no difference in the rate at which BE developed, nor was there a change in the number of precancerous cells in either group. Source: EurekAlert! 9/9/09

Seizure Drug Enhances Sleep for Women with Hot Flashes

Gabapentin, a drug initially used to treat seizures, improves sleep quality in menopausal women with hot flashes, University of Rochester Medical Center researchers report online and in the September issue of the Journal of Women's Health. The study is the first to show sustained benefits in sleep quality from gabapentin, which Rochester researchers already have demonstrated alleviates hot flashes. For the current study, researchers used data from a previously published randomized, double-blind, placebo-controlled trial of gabapentin in 59 postmenopausal women who experienced seven to 20 hot flashes daily. The subjects took either 300 mg of gabapentin three times a day or a placebo. The results showed overall improvement in the sleep quality score, even after 12 weeks of treatment. Gabapentin's impact on the sleep quality factor in menopausal women may reflect improvement in hot flashes, stabilization of sleep architecture, or a decrease in the amount of time to transition from wakefulness to sleep, the researchers wrote. It is also possible that gabapentin improved sleep quality by addressing underlying sleep pathology, such as restless legs syndrome. Source: EurekAlert! 9/8/09

Swine Flu Vaccine Trial Reveals One Dose Provides Strong Immune Response

Results from the first swine flu vaccine trials taking place in the United Kingdom reveal a strong immune response after just one dose. The pilot study, run by the University of Leicester and Leicester Hospitals, involved 100 healthy volunteers, aged between 18 and 50. Dr. Iain Stephenson, who led the trial at the Leicester Royal Infirmary, said: "The clinical trial of Novartis MF59-adjuvanted cell-based A(H1N1) vaccine indicates that the 'swine flu' vaccine elicits a strong immune response and is well tolerated. Results showed that the serum antibody responses were highest among subjects who received two doses of vaccine, however, a single vaccine dose also induced responses associated with protection against influenza. The findings showed that it is possible to induce protective antibody against A(H1N1) infection within two weeks of administration of a single low-dose adjuvanted vaccine." Source: EurekAlert! 9/3/09

Trials Address the Problem of Antimicrobial Resistance

Scientists are addressing the threat of antimicrobial drug resistance by launching two new clinical trials aimed at prolonging the effectiveness of currently available antibacterial drugs. The concept underlying both studies: Less is more. The six-year contracts from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, are part of an initiative intended to help answer key questions about proper antimicrobial doses, treatment duration, and whether antimicrobial treatment is necessary in all cases. NIAID has made an initial award of $1.5 million to the Children's Hospital of Philadelphia with further funding of up to a total of $13.8 million available over the course of the contract if clinical trial milestones are met; investigators will study as many as 1,000 children with urinary tract infections to determine if treatment with antimicrobials can be shortened from the standard length of up to two weeks and still be effective. Duke University in Durham, N.C., has received an initial award of $1.4 million, and if milestones are met, the total award could total up to $11 million over six years; the study also will test the effectiveness of shorter duration of antimicrobial treatment, with a focus on hospitalized patients who acquire staphylococcal infections in the bloodstream after use of an intravenous catheter. NIAID intends to fund additional innovative proposals aimed at slowing the development of antimicrobial resistance through targeted clinical trials, including ones focused on acute ear infections in children, pneumonia, and bloodstream infections caused by Gram-negative bacteria. For more information about this new research initiative, see Targeted Clinical Trials to Reduce the Risk of Antimicrobial Resistance. Source: NIH press release 9/2/09

Therapy Dramatically Improves Response, Survival in Deadly Recurrrent Glioblastomas

The targeted therapy Avastin, alone and in combination with the chemotherapy drug CPT-11, significantly increased response rates, progression-free survival times, and survival rates in patients with a deadly form of brain cancer that had recurred. Early results from the randomized Phase II study prompted the U.S. Food and Drug Administration to agree to an accelerated approval of Avastin in May 2009 for use in patients with recurrent glioblastomas, said Dr. Timothy Cloughesy, director of the Neuro-Oncology Program at the University of California Los Angeles's Jonsson Comprehensive Cancer Center and senior author of the study. The program allows provisional approval of medicines for cancer or other life-threatening diseases. The study, conducted at 11 centers across the county, was published recently in the early online version of the Journal of Clinical Oncology. The two-armed study enrolled 167 patients with recurrent glioblastoma. In the Avastin-only arm, 28.2 percent of patients responded to the treatment, meaning their tumors shrunk by 50 percent or more, a significant increase from the historic 5 percent response rates. Of the 80 patients, 42.6 percent surpassed the six-month mark without their disease progressing, up from the historic 15 to 20 percent of patients. Survival was 9.2 months, a slight increase of the typical six- to seven-month survival time. In the arm studying Avastin with CPT-11, 37.8 percent of patients responded to the treatment, while 50.3 percent surpassed the six-month progression-free survival mark. Overall survival was 8.7 months, a little less than the Avastin-only study. Avastin also appeared to reduce brain swelling, allowing patients to significantly lower the steroid dose they had to take, eliminating a number of debilitating side effects. Other institutions participating in the study included the University of California, San Francisco, M.D. Anderson, Dana Farber, Memorial Sloan-Kettering, Duke University, Henry Ford Hospital, the University of Virginia, the University of Chicago, Evanston Northwestern Healthcare, and the University of Utah Hospital. The study was funded by Genentech, which manufacturers Avastin. Source: EurekAlert! 9/2/09

New Treatment for Hand Disorder Affecting Millions Shows Promise

Researchers in the Department of Orthopaedics at Stony Brook University Medical Center have developed an injectable form of the enzyme, collagenase, that significantly improves outcomes of Dupuytren’s contracture, a debilitating disorder caused by progressive accumulation of collagen that deforms fingers and limits motion. Reported in the New England Journal of Medicine, the study involved treatment of 308 patients with Dupuytren’s disease in 16 sites nationwide. The results indicate that the injections are safe and effective. Collagenase injections may offer an option to hand surgery, the standard treatment. Coprincipal investigators Lawrence C. Hurst, MD, professor and chair of the medical center's Department of Orthopaedics, and Marie A. Badalamente, PhD, professor of orthopaedics, began working with collagenase more than 15 years ago in their laboratory when they first realized the enzyme had potential to treat Dupuytren’s disease. The investigative process has resulted in a bench-to-bedside story that began with successful laboratory results on breaking up collagen within fibroproliferative tissue of the cords. With Food and Drug Administration (FDA) permission, clinical research Phase II trials were conducted in more than 200 patients. By 2007, Drs. Hurst and Badalamente began enrolling patients in a FDA-regulated multicenter Auxilium Pharmaceuticals, Inc. Phase III clinical trial. Other participating institutions enrolling patients in the trial included Stanford Hospitals and Clinics in Palo Alto, Calif., University of California, Los Angeles, the Hospital for Special Surgery in New York, and the Indiana Hand Center in Indianapolis. In Phase III, 308 patients with joint contractures of 20 degrees or more received up to three injections of collagenase or placebo. A total of 203 patients received the collagenase. One day after injection, the joints were manipulated. The goal of the treatment was to achieve a reduction in contracture of zero to 5 degrees of full digit extension within 30 days after the final injection. Patients were evaluated 90 days post-treatment. Upon evaluation, the investigators found that contractures were reduced to zero to 5 degrees of full extension (zero degrees) in nearly two-thirds (64 percent) of joint contractures with collagenase, as compared to 6.8 percent of those placebo-injected. Among all the cords causing joint contracture that were injected with collagenase, 84.7 percent showed improvement, compared to placebo (11.8 percent). In addition, collagenase-injected joint contractures showed a much greater percent reduction in the contracture from baseline to 30 days after the final injection--79.3 percent compared to 11.4 percent, respectively. Source: Newswise 8/28/09

Breast Cancer Trial Examines Shorter Radiation Course

Researchers at the Cancer Institute of New Jersey (CINJ), a part of the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, have launched a clinical trial that focuses on a shorter course of radiation treatment for those with early-stage breast cancer. Studies have shown that giving radiation therapy to the breast after the cancer is removed through surgery (lumpectomy) helps keep the disease from coming back in that area. The current treatment standard is known as whole breast irradiation (WBI), in which radiation is targeted at the entire breast. It is given for five days a week for five to seven weeks. Partial breast irradiation (PBI) is also used, but is only targeted to the area of the breast where the lumpectomy was performed. This treatment is given twice a day for five days. Many patients, however, are not suitable candidates for PBI, and thus require WBI, which can be burdensome for many women due to the length of treatment. In this study, women who are not suitable for PBI alone will receive a shorter course of WBI. The daily radiation dose to be delivered will be higher in the WBI treatment than in the standard course. As New Jersey’s only National Cancer Institute-designated Comprehensive Cancer Center, CINJ offers patients access to treatment options not available at other institutions within the state. CINJ currently enrolls more than 1,000 patients in clinical trials, including approximately 15 percent of all new adult cancer patients and approximately 70 percent of all pediatric cancer patients. Enrollment in these studies nationwide is fewer than five percent of all adult cancer patients. Source: Newswise 8/21/09

Cornell Makes Cancer Vaccine for Clinical Use

The Bioproduction Facility at Cornell University has produced the first batch of NY-ESO-1 recombinant protein—a cancer vaccine—that will be used in clinical trials for patients facing either ovarian cancer or melanoma. The facility was developed as a partnership between the Ludwig Institute for Cancer Research (LICR) and Cornell University. The melanoma trial is being conducted at New York University Medical Center, while the ovarian cancer vaccine trial is being conducted at the Roswell Park Cancer Institute in Buffalo, N.Y. The trials are assessing the safety and the antitumor immune response of the NY-ESO-1-specific therapeutic cancer vaccine alone and in combination with other agents, according to the Cancer Research Institute (CRI), an organization that has recently given $450,000 to Cornell to support vaccine production at the facility. The goal of these trials is to maximize the body's immune response to the NY-ESO-1 protein to fight an existing tumor. The challenge is that the vaccine is made from proteins that are natural to human bodies and do not normally induce strong immune responses. NY-ESO-1 has been the central focus of the CRI/LICR Cancer Vaccine Collaborative, a global network of laboratory and clinical scientists devoted to the development of cancer vaccines. The immune-boosting effect of NY-ESO-1 vaccines has been studied in more than 40 early-phase, single-variable clinical trials. The Cornell NY-ESO-1 protein will be used in other Cancer Vaccine Collaborative clinical trials around the world. Source: EurekAlert! 8/20/09

Detecting Bias in the Reporting of Clinical Trials

A study by researchers at the University of Leicester has revealed new ways to spot whether medical research has hidden biases. Writing in the prestigious British Medical Journal, Santiago Moreno and his colleagues demonstrate how to spot "publication bias" in the reporting of clinical trials that potentially form the basis of national health policies. They also show what mathematical adjustments can be made to remove such unintended distortion of data. According to the theory of publication bias, trials with negative results for a treatment may be less likely to be published than those showing that the treatment does work; this can create a distorted view of the treatment's effectiveness when policy makers have to decide on whether it is worthwhile. The University of Leicester researchers examined two new methods of statistical analysis, using data on antidepressant use available from the United States' Food and Drug Administration. Both methods investigated by the Leicester team proved effective in identifying and eliminating publication bias from medical research. Santiago's colleagues in the research project were Professor Alex Sutton, Professor Keith Abrams and Dr Nicola Cooper, from the Department of Health Sciences, plus collaborators at the Universities of Bristol and Oregon. Source: EurekAlert! 8/19/09

Grant Backs Development of New Treatments for Depression

The University of Illinois at Chicago has received a five-year, $4.8 million federal grant to develop new therapeutics to treat depression. What is needed are antidepressants that work faster, have fewer side effects, and that act pharmacologically in new ways, says Alan Kozikowski, professor of medicinal chemistry and pharmacogonosy and the grant's principal investigator. Kozikowski and his research team had been designing and synthesizing novel nicotine-like compounds that target certain receptors in the brain, in hopes that they would improve cognition in Alzheimer's disease. Studies in animal models revealed that some of these compounds had antidepressant activity. While the main focus of the research now is to develop medications for depression, Kozikowski said it is likely some candidate compounds may have other clinical applications, including the treatment of schizophrenia, pain, and nicotine dependence. In fact, the drug discovery group--which also includes investigators from the Barrow Neurological Institute in Phoenix and from PsychoGenics Inc. in Tarrytown, N.Y.--has already found that some of these novel agents do work for pain in animal models. Meanwhile, studies suggest that nicotinic compounds that have been modified to reduce their addictive potential while retaining the ability to balance mood could provide a new family of antidepressant drugs. In spite of the intensive efforts that have gone into the design and study of nicotinic drugs, very few of the compounds have reached clinical trials, Kozikowski said. The new grant is part of the National Cooperative for Drug Discovery and Development Groups and is funded by the National Institute of Mental Health, one of the National Institutes of Health. Source: Newswise 8/18/09

Britain's First Swine Flu Trials Under Way

Britain's first swine flu vaccine trials, led by the University of Leicester and University Hospitals of Leicester National Health Service Trust, are taking place at the Leicester Royal Infirmary. Dr. Iain Stephenson, a consultant in infectious diseases at the hospital and clinical senior lecturer at the university, has been carrying out research into swine flu and has published academic papers on the subject. Now he is working with 175 volunteers, aged 18 to 50, as part of research to develop a vaccine against the virus. The volunteers were recruited in the last week of July, and blood samples are now being taken to detect how much immunity the drug gives. Earlier research by Stephenson and colleagues already established that two doses of the vaccine would be needed to build up immunity. Results from the trials are expected in September. Source: EurekAlert! 8/11/09

Discovery Could Help Stem Parasitic Roundworm Infections

Working with researchers in China, biologists at University of California San Diego (UCSD) have discovered how a Chinese drug effective in killing parasitic roundworms works. Their discovery of the drug's biological mechanism provides important new information about how to combat parasitic roundworms, which infect more than a billion people in tropical regions and are one of the leading causes of debilitation in underdeveloped countries. The researchers detail their findings in the current issue of the open-access journal PLoS Neglected Tropical Diseases. "For practical reasons, only one drug, albendazole, is now widely used in administering single-dose treatments to large populations," said Raffi Aroian, a professor of biology at UCSD who headed the research effort. "But because of the enormous numbers of people that need to be treated and the necessity of repeated treatments due to high re-infection rates, the development of resistance to albendazole is a serious threat to large-scale deworming efforts. We are studying this Chinese drug, tribendimidine, that clinically appears to be as good as albendazole." Developed by the Chinese Center for Disease Control and Prevention in Shanghai, tribendimidine has not yet been approved for human use. Recent clinical trials in China and Africa have found the drug to be effective in humans against some roundworm parasites, such as hookworms. However, not much is known about the biological mechanisms by which the drug kills roundworms or the biochemical pathways through which roundworms can develop resistance to tribendimidine. "This information is important for preventing, detecting, and managing the resistance that some organisms can evolve to drugs," said Aroian. "It's also important in order to safely administer the drug to large populations and for knowing how to combine tribendimidine with other drugs." The researchers were supported in their study by grants from the National Institutes of Health. Source: EurekAlert! 8/10/09

Collaboration to Focus on Preclinical Research and Clinical Trials for Cancer Treatments

EMD Serono, Inc. and the University of Texas M. D. Anderson Cancer Center in August announced a strategic alliance designed to provide M. D. Anderson with early insight into potential cancer treatments and to accelerate EMD Serono's preclinical and early clinical research to ultimately bring new drugs to patients faster. The agreement is set for three years with the potential to renew the alliance. This nonexclusive strategic alliance will collaboratively draw on the expertise and resources of M. D. Anderson and EMD Serono to help design and conduct clinical trials for EMD Serono's oncology product candidates. Dr. Bernhard Kirschbaum, executive vice president for research and development at Merck Serono, said,"We hope that through this alliance we are able to initiate important clinical trials faster and more efficiently to fully exploit our rich oncology pipeline." Dr. Robert Bast, MD, PhD, vice president for translational research at M. D. Anderson, added, "We believe there are many opportunities within this alliance to further expand both organizations' research initiatives and programs within oncology to bring more effective treatments to our patients." In 2008, nearly 13,000 M. D. Anderson patients participated in clinical trials exploring novel treatments, the largest such program in the nation. The collaboraters plan to focus on which Phase I clinical trials will benefit from the strategic alliance, and expect to begin patient enrollment for selected trials in 2009. Source: PRNewswire 8/10/09

First Human Gets New Antibody Aimed at Hepatitis C Virus

Building on a series of successful preclinical studies, researchers at MassBiologics of the University of Massachusetts Medical School in August announced the beginning of a Phase I clinical trial to test the safety and activity of a human monoclonal antibody they developed that can neutralize the hepatitis C virus (HCV). The first volunteer received the antibody, known as MBL-HCV1, on July 28; the study is now proceeding and will eventually involve 30 healthy subjects in a dose-escalation trial expected to conclude later this year. "We are pleased that this program has now entered the clinical trial phase," said Donna Ambrosino, MD, executive director of MassBiologics and a professor of pediatrics at the medical school. "This trial will test the safety of the antibody and measure its activity in the subjects. This will help us determine the useful dose and other parameters as we plan for the next step in this program, which will be a Phase II study in liver transplant patients." The new antibody is designed to be a therapy shortly before and after transplant surgery. By giving a patient the new antibody before and during the time when the donor liver is implanted, researchers hope the HCV virus left in the bloodstream will be neutralized and rendered unable to infect the new liver. Source: EurekAlert! 8/6/09

Drug May Offer Hope for Children with High-Risk Leukemia

Tel Aviv University researchers who discovered a mutation of the JAK2 protein in patients with Down syndrome suspected that this protein might also be linked to other disorders and diseases--and they were right. Based on the successful results of the team's research, a drug that is already in clinical trials for a blood disease common in adults may be relevant for acute childhood leukemia. If initial trials go well, the drug could fast-track through approvals and could be available for treating children with leukemia in only a few years. A similar mutation of the JAK2 in Down syndrome and leukemia causes polycythemia vera, a disease common in adults that leads to the overproduction of blood. Because of the existence of polycythemia in adults, there are already drugs to fight polycythemia entering into trials. The researchers expect to know in just a few years what these drugs are capable of. JAK2 inhibitors are not based on chemotherapy. The first experiences with these treatments show very few side effects. All that researchers need to do is to expand these clinical trials to children and adults with high-risk leukemia--and that could happen relatively quickly. Source: EurekAlert! 7/28/09

Hepatitis C Infection: Treatment Options Equally Effective

Results of a long-awaited study of 3,070 American adults at Johns Hopkins and 118 other U.S. medical centers show that treatment with either of the two standard antiviral drug therapies is safe and offers the best way for people infected with hepatitis C to prevent liver scarring, organ failure, and death. A report on the comparative effectiveness study, believed to be the largest of its kind conducted on people with hepatitis C infections, appeared in the New England Journal of Medicine online July 22. "When considering treatments for hepatitis C infection, patients and their doctors now have solid evidence that they can weigh both antiviral therapies equally for effectiveness, safety, and tolerability," says study coprincipal investigator Mark Sulkowski, MD, medical director of Johns Hopkin Center for Viral Hepatitis. In a surprise finding, the researchers say, the study found no major difference between the only two U.S. Food and Drug Administration-approved drug treatment regimens in suppressing the virus to undetectable levels in the blood. Either of the two standard, 48-week, dual drug therapies--peginterferon alfa-2b, plus ribavirin, or peginterferon alfa-2a, plus ribavirin--worked equally well, at 39.8 percent and 40.9 percent, respectively. Funding support for this study, which took place between March 2004 and June 2006, was provided by the Schering-Plough Corp., the brand manufacturer and provider of study drugs ribavirin and peginterferon alfa-b. Peginterferon alfa-a is manufactured by Hoffman La Roche Inc. Source: Newswise 7/22/09

Clinical Study Targets Protein Misfolding

Discoveries by Scripps Research Institute scientists have led to a promising new drug candidate--the first in its class--for patients with a genetic protein-misfolding disease. In results announced by the biopharmaceutical firm FoldRx Pharmaceuticals, Inc. in July, the new drug tafamidis significantly halts disease progression for patients with a disease called Transthyretin (TTR) amyloid polyneuropathy, also known as Familial Amyloid Polyneuropathy, a slowly progressive, multifaceted disease that causes loss of sensation, muscle weakness, and autonomic nerve dysfunction (including gastrointestinal disorders and urinary problems), ultimately leading to death. The only treatment currently available is liver transplantation. The results from FoldRx's randomized, controlled Phase II/III clinical study show once-daily oral treatment with tafamidis significantly halts disease progression and reduces the burden of disease after 18 months compared to placebo. The study also showed that tafamidis appears to be safe and well tolerated. In TTR amyloid polyneuropathy, the protein transthyretin "misfolds," and amyloid fibrils cluster in peripheral nerve tissues that serve limbs and organs. The research was made possible by the financial support of the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, the Skaggs Institute for Chemical Biology at Scripps Research, and the Lita Annenberg Hazen Foundation, among other organizations. Source: EurekAlert! 7/21/09

Drug Candidate Prolongs Lives of Pancreatic Cancer Patients

Every year, 42,000 Americans are diagnosed with pancreatic cancer. Few live very long, and less than 5 percent are still alive five years after diagnosis. There is new hope, however, from the lab of Prof. Yoel Kloog, dean of Tel Aviv University's Faculty of Life Sciences. His drug compound salirasib has shown positive results against pancreatic cancer, and recently passed Phase I/II clinical trials. The drug, given in combination with gemcitabine, the standard drug used to combat pancreatic cancer, almost doubled the life expectancy of those who received it. Salirasib works by inhibiting a protein called Ras, which is known to be abnormally activated in one-third of human cancers. In cancer of the pancreas, mutant forms of Ras are found in up to 90 percent of all tumors. Salirasib's basic component, FTS, works to block the formation of cancer-promoting Ras nanoclusters, thus blocking a cascade of biochemical signals known as the "Ras signaling pathway" that allow Ras to wreak havoc on the body. In the latest study, researchers tested for both toxicity and effectiveness. They gave 19 patients with advanced pancreatic cancer daily doses of salirasib along with a standard gemcitabine regimen. Salirasib was well tolerated by the patients, and they surpassed on average the number of months they would have lived on gentamiacine alone. For this study, salirasib was licensed by Concordia Pharmaceuticals, which collaborated with the Memorial Sloan Kettering Cancer Center, Johns Hopkins, the M.D. Anderson Cancer Center, and other institutes in the United States. If Phase II/III trials are successful, the drug will be the first successful Ras antagonist known to medical science. Source: EurekAlert! 7/20/09

Hospital is First in Country to Enroll Patient in Study for Recurrent Chest Wall Breast Cancer

Rhode Island Hospital is one of only four sites across the country to participate in a new clinical trial called the DIGNITY Study. The study will investigate the effectiveness of a chemotherapeutic agent, ThermoDox, used in conjunction with mild hyperthermia (a form of heat therapy) for treating recurrent chest wall (RCW) breast cancer, which most commonly presents in skin overlying mastectomy scars. The DIGNITY study will test 100 patients nationally. Rhode Island Hospital was the first to enroll and treat a patient. That patient has undergone the first three of a six-cycle course of treatment. Brigid O'Connor, MD, PhD, a radiation oncologist at Rhode Island Hospital, is the principal investigator for the trial in Rhode Island. According to O'Connor, "We treated our first patient recently and she tolerated the procedure well. I am excited to see her response to this new treatment." She continues, "The rapid development of ThermoDox is warranted so we can provide these women who are experiencing recurrent chest wall cancer with a better treatment for this devastating disease. We look forward to the outcomes of this trial in the hope of gaining increased local tumor control and improved quality of life for our patients." To be eligible for participation in the trial, patients must have a confirmed diagnosis of RCW disease, had prior radiation to their chest wall, and received two chemotherapy regimens. The study is sponsored by Celsion Corp. Recruitment for the study is ongoing. Source: EurekAlert! 7/20/09

Study Offers Insights Into Failed HIV-1 Vaccine Trial

Following the disbandment of the STEP trial to test the efficacy of the Merck HIV-1 vaccine candidate in 2007, the leading explanation for why the vaccine was ineffective--and may have even increased susceptibility to acquiring the virus--centered on the hypothesis that high levels of baseline Ad5-specific neutralizing antibodies may have increased HIV-1 acquisition among the study subjects who received the vaccine by increasing Ad5-specific CD4+ T-cells that were susceptible to HIV-1 infection. Now, a study by Dan Barouch, MD, PhD, and a scientific team at Beth Israel Deaconess Medical Center (BIDMC), reported in the July 20 online issue of Nature Medicine, shows this was likely not the case. "Our findings demonstrate that there is no correlation between Ad5 neutralizing antibodies and T-cell immune responses," explains Barouch, who is chief of the Division of Vaccine Research at BIDMC and associate professor of medicine at Harvard Medical School. "Moreover, subjects with baseline Ad5-specific neutralizing antibodies did not develop higher levels of Ad5-specific T-cell responses as compared with subjects without baseline Ad5-specific neutralizing antibodies. ...It does not appear that the potential enhancement of the HIV-1 infection in the STEP study was the result of ... secondary, vector-specific CD4+ T-cell responses." Going forward, Barouch suggests another alternative. "Safety considerations, including the possibility that vector-specific cellular immunity may impact HIV-1 susceptibility, have become major concerns for the HIV-1 vaccine field," he notes. "Our findings suggest a path forward for HIV-1 vaccine development by using rare serotype vectors [not typically found in the general population] that are not suppressed by high levels of baseline vector-specific neutralizing antibodies." Barouch and colleagues are currently conducting Phase I clinical trials to test two such novel HIV-1 vaccines. This study was supported by the Bill & Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery and the National Institutes of Health. Source: EurekAlert! 7/20/09

New Method May Accelerate Drug Discovery for Difficult Diseases

Whitehead Institute scientists have developed a rapid, inexpensive drug-screening method that could be used to target diseases that until now have stymied drug developers, such as Parkinson’s disease. This technique uses baker’s yeast to synthesize and screen the molecules, cutting target discovery and preliminary testing time to a matter of weeks. The current drug discovery process is arduous, requiring identification of potential drug targets, synthesis of large collections of molecular compounds that might interact effectively with an identified target, screening of compounds with expensive assays and robotics, and defining the compounds’ structures largely through trial and error. At the end of this months-long process, a large team of chemists and biologists usually deem only 1 percent or less of the compounds worthy of further testing in living cells. A novel method, demonstrated by Whitehead scientists and described in the July 13 issue of Nature Chemical Biology, uses baker’s yeast cells to perform most of the same work in a matter of weeks, with the added benefit that the testing is all done in living cells. At the core of this approach are extremely small proteins, called cyclic peptides, which are capable of targeting the protein-protein interactions found in almost every cellular process. Most current drugs act by wedging themselves into small pockets on the surfaces of target proteins. However, these traditional drugs are unable to adhere to smooth, flat protein surfaces, rendering the drugs ineffective for inhibiting the key interactions among proteins that occur at these surfaces. Cyclic peptides have the ability to bind where traditional drugs cannot, allowing for the identification of previously overlooked targets to fight disease. This study was funded by National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences, and the Morris K. Udall Centers of Excellence for Parkinson’s Disease Research. Source: Newswise 7/13/09

Medical Center Participating in Avastin Trial for New Glioblastoma Patients

The Derrick L. Davis Forsyth Regional Cancer Center at Forsyth Medical Center in Winston-Salem, N.C., is participating in a national trial of the experimental drug Avastin to treat glioblastoma, a fast-growing tumor of the brain or spinal cord. The center is participating in the third phase of the trial, testing the effectiveness of Avastin in conjunction with standard chemotherapy and radiation treatments for patients newly diagnosed with glioblastoma. This phase of the trial will enroll 700 participants nationwide, and the center is one of the first sites in the country to participate. The trial is part of the hospital's neurosciences program. "Avastin has been shown to be effective in treating various types of cancer, with a low risk of serious side effects, so our hope is that it will improve outcomes for patients with brain tumors when it is added to standard-of-care treatments," says Volker Stieber, MD, a radiation oncologist at the center. "Phase III is the highest level of research for a drug, so we are excited to be part of a study that could advance treatment for patients with this type of cancer." In May, the U.S. Food and Drug Administration approved the use of Avastin to treat glioblastomas that have not responded to other therapies, based on results from two Phase II studies that showed Avastin reduced tumor size in some glioblastoma patients. The new study evaluates this drug in newly diagnosed, never-treated glioblastoma patients. The center is currently screening patients for enrollment in the clinical trial. Eligible patients may qualify if they are newly diagnosed adults able to undergo partial removal of their tumors. Once enrolled, participants will remain in the study for up to one year. Source: EurekAlert! 7/8/09

Clinical Trial Shows Tongue Drive System Assists Disabled

An assistive technology that enables individuals to maneuver a powered wheelchair or control a mouse cursor using simple tongue movements can be operated by individuals with high-level spinal cord injuries, according to the results of a recently completed clinical trial. “This clinical trial has validated that the Tongue Drive system is intuitive and quite simple for individuals with high-level spinal cord injuries to use,” said Maysam Ghovanloo, an assistant professor in the School of Electrical and Computer Engineering at the Georgia Institute of Technology. “Trial participants were able to easily remember and correctly issue tongue commands to play computer games and drive a powered wheelchair around an obstacle course with very little prior training.” At the annual conference of the Rehabilitation Engineering and Assistive Technology Society of North America in June, the researchers reported the results of the first five clinical trial subjects to use the Tongue Drive system. The trial was conducted at the Shepherd Center, an Atlanta-based catastrophic care hospital, and funded by the National Science Foundation and the Christopher and Dana Reeve Foundation. At the beginning of each trial, Ghovanloo and graduate students Xueliang Huo and Chih-wen Cheng attached a small magnet--the size of a grain of rice--to the participant’s tongue with tissue adhesive. Movement of this magnetic tracer was detected by an array of magnetic field sensors mounted on wireless headphones worn by the subject. The sensor output signals were wirelessly transmitted to a portable computer, which was carried on the wheelchair. The signals were processed to determine the relative motion of the magnet with respect to the array of sensors in real-time. This information was then used to control the movements of the cursor on a computer screen or to substitute for the joystick function in a powered wheelchair. Details on use of the Tongue Drive for wheeled mobility were published in the June 2009 issue of the journal IEEE Transactions on Biomedical Engineering. Source: Newswise 7/6/09

European Researchers Look for New Ways to Fight Multidrug-Resistant Bacterial Infections

The Institute of Biotechnology and Biomedicine at Universitat Autònoma de Barcelona is directing a four-year research project to look for new drug targets in pathogenic bacteria resistant to multiple antibiotics. To support the effort, a consortium was created by six institutions and firms in Spain, three in Germany, one in France, and one in Bulgaria. The AntiPathoGN project intends to cover the need for more knowledge of the biological processes and cell growth and division mechanisms of four of the most resistant gram-negative bacteria--Pseudomonas aeruginosa, Helicobacter pylori, Acinetobacter baumannii, and Escherichia coli. These bacteria cause respiratory, digestive, urinary tract, skin, and many other types of infections. The project works with a multidisciplinary approach and includes innovative contributions from the fields of microbiology, proteomics, computational and structural biology, and pharmaceutics. The AntiPathoGN project is coordinated by Xavier Daura, a professor at the Barcelona university. Other participating institutes are the Institute for Biomedical Research in Barcelona, the Clinical Foundation for Biomedical Research, and the biotechnology firms Infociencia, Anaxomics Biotech, and Microbionta. Source: EurekAlert! 6/25/09

Compound Increases Endurance Without Regular Exercise Training

Quercetin may not be a household word--yet. However, a study by researchers at the University of South Carolina’s Arnold School of Public Health shows that the powerful antioxidant/anti-inflammatory compound found in fruits and vegetables significantly boosts endurance capacity and maximal oxygen capacity (VO2max) in healthy, active, but untrained men and women. The findings of the study--one of the first in humans to examine the energy-boosting effects of quercetin--are reported in the International Journal of Sports Nutrition and Exercise Metabolism, published online June 24. Dr. Mark Davis, the study’s lead author and a professor of exercise science, said the fatigue-fighting and health properties of quercetin--found in the skins of red apples, red onions, berries, and grapes--have implications not only for athletes and soldiers whose energy and performance are tested to the extreme, but also for average adults who battle fatigue and stress daily. “While there’s no magic pill to make people get up and move, or to take the place of regular exercise, quercetin may be important in relieving the fatigue that keeps them sedentary and in providing some of the benefits of exercise,” Davis said. For the study, funded in part by the U.S. Department of Defense, 12 participants were randomly assigned to one of two treatments. Half were given 500 mg of quercetin twice a day in Tang for seven days. The other subjects drank Tang with placebos. After the seven days of treatment, during which the subjects were told not to alter their physical activity, the participants rode stationary bicycles to the point of fatigue. Researchers also tested their additional VO2max, one of the most important measures of fitness. Then the participants received the opposite treatment for another seven days before riding the bicycle to the point of fatigue and VO2max tests. Neither the participants nor the research staff knew who received the quercetin Tang or the placebo Tang, and all subjects took part in the quercetin and placebo treatments. After taking quercetin for only seven days, the participants had a 13.2 percent increase in endurance and a 3.9 percent increase in VO2max. Although the study did not examine why the results were so dramatic, Davis said preclinical data suggest that quercetin may increase the mitochondria in brain and muscle cells. Source: Newswise 6/24/09

$48 Million in Grants Go to Study of Catheter Ablation for Atrial Fibrillation

Mayo Clinic received $48 million in grants from the National Heart, Lung, and Blood Institute (NHLBI), a component of the National Institutes of Health (NIH), and from industry to study the treatment of atrial fibrillation in 3,000 patients and 140 centers around the world. Mayo Clinic is leading the study. The Catheter Ablation Versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation (CABANA) trial is designed to determine whether catheter ablation is more effective than drug therapy for the treatment of atrial fibrillation, says Douglas Packer, MD, the trial's principal investigator and a cardiologist at Mayo Clinic. The study, which will take six years from beginning to releasing results, is a collaborative effort among Dr. Packer and Richard Robb, PhD, at Mayo Clinic, Kerry Lee, PhD, and Daniel Mark, MD, at Duke Clinical Research Institute in Durham, N.C., and the NHLBI. Funding for the trial consists of $18 million from NHLBI/NIH, $20 million from St. Jude Medical, and $10 million from Biosense Webster. The study will randomize patients over three years, with half undergoing catheter ablation and half receiving rate control or rhythm control drug therapy (used to keep the heart in normal rhythm). Before these grants were awarded, Mayo Clinic led a 10-center, 60-patient pilot study. Those results will be announced later this summer. Source: EurekAlert! 6/12/09

Can Lowering Body Temperature Prevent Brain Damage in Children?

In the first large-scale study of its kind, researchers at the University of Michigan's C.S. Mott Children's Hospital and the University of Utah will lead a multicenter study to investigate whether hypothermia--lowering body temperature--can prevent or reduce brain damage in children deprived of oxygen after a cardiac arrest. The Therapeutic Hypothermia After Pediatric Cardiac Arrest (THAPCA) trials begin this fall. The National Heart, Lung, and Blood Institute, part of the National Institutes of Health, will provide funding for the Vanguard phase, and pending successful completion of that phase, for a total of six years of subject accrual from 30 trial sites, and up to 900 participants in the United States and Canada. Frank W. Moler, MD, MS, medical director of the Mott pediatric intensive care unit and professor of pediatrics at the University of Michigan Medical School, is the scientific principal investigator, while J. Michael Dean, MD, MBA, HA, a professor of pediatrics at the University of Utah School of Medicine and Primary Children's Medical Center, Salt Lake City, is principal investigator for the data center. Every year, thousands of children suffer cardiac arrest as complications from illnesses or as the result of accidents, such as near-drowning. The THAPCA trials will look at children who experience cardiac arrest while already hospitalized for another condition or disease, and those who have cardiac arrest after an event or sudden illness outside the hospital. Children in the trials will be randomly assigned into two actively managed therapy groups: those whose body temperatures will be lowered to 32-34 degrees C through surface cooling called therapeutic hypothermia, and those whose body temperatures are actively kept in the normal range 36-37.5 degrees C, also by surface cooling, sometimes called therapeutic normothermia. Source: EurekAlert! 6/11/09

Artificial Pancreas Proves Effective in Treating Type 1 Diabetes

Researchers at the University of Virginia Health System are reporting remarkable results from their pilot clinical study of the artificial pancreas, a computerized, subcutaneous system that could one day revolutionize the way Type 1 diabetics manage their disease. The system, which uses an individually “prescribed” control algorithm to regulate blood glucose levels, achieved excellent overnight control of glucose levels in Type 1 diabetics and a five-fold reduction of hypoglycemia. “These are the first substantial results from our ongoing clinical studies, and they are very encouraging,” says Boris Kovatchev, PhD, an associate professor in the university's School of Medicine and lead investigator of the research team. Kovatchev and fellow researchers presented their findings in June at the American Diabetes Association’s 69th Scientific Sessions in New Orleans, La. Over the past year, researchers have successfully tested the new system on a total of 20 Type 1 diabetic patients--11 in Virginia; six at the University of Pavova, Italy; and three at the University of Montpellier, France. The University of Virginia is one of seven centers worldwide funded by the Juvenile Diabetes Research Foundation to perform the novel closed-loop computer simulation of the human metabolic system. For the clinical trials, each patient underwent two 24-hour hospital admissions, in which the patient had identical eating, sleeping, and activity patterns during both admissions. During the first admission, patients controlled their own blood sugar levels in open-looped, physician-supervised sessions. The second admission involved the closed-loop, automated system controlling patients’ glucose levels. This was achieved by researchers programming the system’s algorithm with personalized glucose data obtained from the patient’s previous admission. Results from each patient’s admissions then were compared to determine differences in glucose control. The researchers found an overall decrease from 23 episodes of hypoglycemia during the open-loop sessions to five during closed-loop control. Furthermore, researchers found that nearly 100 percent of all overnight data from the closed-loop sessions were within the target range of 70 to 180 mg/dl, and the time patients spent with blood glucose levels falling within the narrower 70 to 140 mg/dl range increased from 65 percent to 78 percent from open-loop to closed-loop control. Source: Newswise 6/8/09

Brain-Computer Interface Begins New Clinical Trial

BrainGate, an investigational technology being developed to detect brain signals and to allow people with paralysis to use those signals to control assistive devices, is about to begin a second, larger clinical trial. The system is based on neuroscience, engineering, and computer science research at Brown University. The BrainGate2 pilot clinical trial is taking place at Massachusetts General Hospital (MGH), in close collaboration with an interdisciplinary team of researchers from MGH and Brown University. The study has been approved by the MGH Institutional Review Board to begin recruiting participants. The trial extends prior safety and feasibility research of the BrainGate Neural Interface System, which consists of an implanted baby aspirin-size brain sensor that reads brain signals and computer technology that interprets these signals. The Brainate Neural System may allow people with paralysis to control assistive devices. The new clinical trial is part of a larger BrainGate research effort, the ultimate goal of which is to help patients with spinal cord injury, stroke, muscular dystrophy, amyotrophic lateral sclerosis, or limb loss turn their thoughts into actions, restoring independence, mobility, and communication. The work to date with BrainGate trial participants has explored their ability to control robotic limbs, operate computer software, and drive a wheelchair. New research will help advance the pilot system. A previous clinical trial run by Cyberkinetics Neurotechnology Systems Inc., together with researchers at MGH and Brown, demonstrated that the neural signals associated with the intent to move a limb can be "decoded" by a computer in real time and used to operate external devices. For financial reasons, Cyberkinetics stopped funding the trial and withdrew from the research. The new research is funded entirely by the National Institutes of Health, the U.S. Department of Veterans Affairs, and philanthropic sources. This research is based on work supported in part by the Office of Research and Development, Rehabilitation R&D Service, Department of Veterans Affairs. Source: EurekAlert! 6/10/09

Common Chemotherapy Drug Can Trigger Fatal Allergic Reactions

A chemotherapy drug that is supposed to help save cancer patients' lives can instead result in life-threatening and sometimes fatal allergic reactions. A new study from the Research on Adverse Drug Events and Reports (RADAR) pharmacovigilance program at Northwestern University Feinberg School of Medicine identified 287 unique cases of hypersensitivity reactions submitted to the Food and Drug Administration's Adverse Event Report System between 1997 and 2007 with 109 (38 percent) deaths in patients who received Cremophor-based paclitaxel, a solvent-administered taxane chemotherapy. The severe allergic reactions are believed to be caused by Cremophor, the chemical solvent--a derivative of castor oil--that is used to dissolve some insoluble drugs before they can be injected into the blood stream. Two patients who died from an allergic reaction had early-stage breast cancer, which had been surgically removed, and were being treated with Cremophor-containing paclitaxel to prevent the cancer from coming back. Both of these patients had received medications before the chemotherapy to reduce the risk of hypersensitivity reactions. The study was led by Charles Bennett, MD, RADAR program coordinator and a professor of hematology/oncology at Northwestern's Feinberg School, and Dennis Raisch, a professor of pharmacy at the University of New Mexico. "The deaths of women with early-stage breast cancer are particularly disturbing because without the adverse reaction, they could have likely had 40 years of life ahead of them," Bennett said. RADAR investigators also found that 22 percent of all fatalities occurred in patients despite their having received premedication to prevent hypersensitivity reactions, while another 15 percent of such patients experienced life-threatening respiratory arrest. The report was presented at the 45th Annual Meeting of the American Society of Clinical Oncology, held recently in Orlando, Fla. Source: EurekAlert! 6/8/09

First Heart Patients Implanted with Next-Generation Mechanical Heart Pump

Three patients at NewYork-Presbyterian Hospital/Columbia University Medical Center were among the first in the United States to be implanted with a next-generation artificial heart pump called the DuraHeart™ Left-Ventricular Assist System. The surgeries took place earlier this year. NewYork-Presbyterian/Columbia is one of only three centers in the U.S. currently enrolling patients in a clinical trial studying the device. The DuraHeart is designed to sustain patients with severe left-ventricular heart failure while they wait for a heart transplant. The surgeries were led by Dr. Yoshifumi Naka, director of cardiac transplantation at NewYork-Presbyterian Hospital/Columbia University Medical Center and associate professor of surgery at Columbia University College of Physicians and Surgeons. He elected to implant the device without stopping the heart and putting the patient on a heart-lung machine. This "off pump" approach reduces risk for bleeding and stroke associated with putting a patient on bypass. "In this clinical trial, we hope to show that this device can help patients retain a healthy and meaningful quality of life while awaiting a heart transplant," says Dr. Naka, one of three national coprincipal investigators of the DuraHeart trial. "Eventually, the DuraHeart may also prove to be a long-term solution, even for those ineligible for transplantation." The DuraHeart trial will ultimately enroll 140 patients in up to 40 centers nationwide. The trial is designed for end-stage heart failure patients that have been placed on a heart transplant list in the U.S. The trial is sponsored by Terumo Heart Inc. of Ann Arbor, Mich., maker of the DuraHeart System and a wholly owned subsidiary of Terumo Corporation of Tokyo, Japan. Source: EurekAlert! 6/2/09

Grant Funds Groundbreaking Clinical Trial for Earlier Cancer Diagnoses

A first-of-its-kind clinical trial exploring a way to diagnose cancer in its earliest stages is being conducted at the University of Arkansas for Medical Sciences' (UAMS) Winthrop P. Rockefeller Cancer Institute through a National Cancer Institute grant totaling nearly $1.5 million. The five-year grant was awarded to Vladimir Zharov, PhD, professor and director of the Phillips Classic Laser and Nanomedicine Laboratories at UAMS. “To the best of our knowledge, this will be the first clinical application of nanomedicine-based technology for noninvasive detection of circulating tumor cells,” Zharov said. James Y. Suen, MD, chairman of the UAMS Department of Otolaryngology–Head and Neck Surgery, and Laura Hutchins, MD, a professor and director of the Division of Hematology/Oncology in the UAMS College of Medicine, also will participate in the trial. The team is exploring a concept of nanomedicine based on the natural creation of nanoparticles in living cells. These have intrinsic properties to aid the earlier detection of the most aggressive melanoma malignancy that progresses to the incurable metastasis at a very early stage of disease. The clinical trial builds on a technique known as in vivo photoacoustic flow cytometry, previously developed by Zharov and colleague Ekaterina Galanzha. The technique allows researchers to identify and count a wide range of cell types, including those related to cancer, infection, cardiovascular disease, and the body’s immune system. With this grant, the team will focus on detecting so-called circulating tumor cells that might predict if the tumor will spread from the original site to neighboring blood vessels and occur as tumors in other parts of the body. Zharov’s team will determine whether this new treatment is effective enough to be used alone, or if it should be used in conjunction with gold nanoparticles and conventional chemo and radiation therapy. Source: Newswise 5/27/09

Diabetes Drug Shows Promise Against Multiple Sclerosis

A drug currently approved by the Food and Drug Administration for use in diabetes shows some protective effects in the brains of patients with relapsing remitting multiple sclerosis (MS), researchers at the University of Illinois at Chicago College of Medicine report in a study currently available online in the Journal of Neuroimmunology. In a small, double-blinded clinical trial, patients with relapsing remitting MS were assigned to take pioglitazone (a drug commercially known as Actos used to treat Type 2 diabetes) or a placebo. Patients continued their normal course of therapy during the trial. Standard neurological tests were done initially, as were MRI scans to provide baseline values for lesions typically seen in MS patients. The patients were evaluated every two months, and blood samples were taken. Repeat MRI scans were done after five months and again after one year. Patients taking pioglitazone showed significantly less loss of gray matter over the course of the one-year trial than patients taking placebo. Twenty-one patients completed the study. The researchers hope to expand into a larger trial to confirm their preliminary results. Takeda Pharmaceuticals funded the study and provided the drug, but had no other involvement in the study. Source: EurekAlert! 5/26/09

Radiofrequency Ablation Found Effective for Barrett's Esophagus

A landmark clinical trial led by a University of North Carolina at Chapel Hill researcher concludes that radiofrequency ablation (RFA) is an effective treatment for dysplasia in people with Barrett's esophagus, a condition that can lead to deadly gastrointestinal cancer. The study is published in the May 28 issue of the New England Journal of Medicine. Barrett's esophagus is a condition in which repeated acid reflux causes the cells that normally line the esophagus to be replaced by a different type of cell, similar to those normally found in the intestines (intestinal metaplasia). By itself, Barrett's is not a life-threatening problem, but a small percentage of people with Barrett's will develop esophageal adenocarcinoma, an especially deadly form of cancer. RFA, a noninvasive technique that uses thermal energy to destroy cells, is very effective at destroying abnormal cells in the esophagus. The new study is the first randomized trial to evaluate RFA for treating dysplasia, a more advanced stage of Barrett's esophagus in which the abnormal cells acquire precancerous traits. The RFA system used in the study uses thermal energy provided by a set of electromagnetic coils on the surface of a balloon that is inflated in the area of the esophagus with the offending cells. In the study, 127 people were randomized to receive either RFA or a simulated version of the procedure at one of 19 participating medical centers. Overall, 77.4 percent of study participants treated with RFA had complete eradication of intestinal metaplasia, compared to 2.3 percent in the sham group. The study concluded that RFA demonstrated a high rate of eradication of dysplasia and intestinal metaplasia, and that these changes reduced the risk of progression toward dysplasia and the risk of developing cancer. Funding for the study was provided by BARRX Medical Inc., which manufactures the HALO360 RFA system used in the study, the Investigator-Sponsored Study Program of AstraZeneca, and a grant from the National Institutes of Health. Source: EurekAlert! 5/27/09

New Therapy Enlists Immune System to Boost Cure Rate in a Childhood Cancer

A multicenter research team has announced encouraging results for an experimental therapy using elements of the body's immune system to improve cure rates for children with neuroblastoma, a challenging cancer of the nervous system. John M. Maris, MD, chief of Oncology at the Children's Hospital of Philadelphia, coauthored the Phase III clinical trial, which was led by Alice Yu, MD, PhD, of the University of California, San Diego. Maris chairs the committee supervising the trial for the Children's Oncology Group, a cooperative organization that pools resources from leading medical centers to study and devise new treatments for pediatric cancers. The American Society of Clinical Oncology published the findings online on May 14. In the study, researchers studied 226 children with high-risk neuroblastoma. Half received the immunotherapy, while half received standard therapy (chemotherapy and stem cell transplantation). The patients who received the immunotherapy were 20 percent more likely than those in the standard therapy group to live disease-free two years after treatment. The researchers halted the trial earlier than expected after early results showed the benefits of immunotherapy. The supply of the antibodies and cytokines used in the trial was limited, and pediatric oncologists are seeking biotechnology companies to move the biological agents into commercial production to make the treatment readily available to children with neuroblastoma. Source: EurekAlert! 5/27/09

Less-Toxic Drug Prolongs Survival in Metastatic Breast Cancer

Research from the Northwestern University Feinberg School of Medicine has found that a less toxic, solvent-free chemotherapy drug more effectively prevents the progression of metastatic breast cancer and has fewer side effects than a commonly used solvent-based drug. A national study led by William Gradishar, MD, director of breast medical oncology at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, found that the drug Abraxane prolonged progression-free survival by almost seven months compared with Taxotere, which is part of a class of solvent-based drugs called taxanes. The study was published May 26 in the Journal of Clinical Oncology. Chemotherapy drugs need to be dissolved in a chemical, called the "delivery system," before they can be injected into the blood stream. Abraxane uses albumin, a human protein, to deliver the chemotherapy. It does not contain chemical solvents. The generic name for Abraxane is nab-paclitaxel. The study showed Abraxane also was much less toxic to patients. Gradishar said solvents are responsible for many of the side effects of chemotherapy, including a drop in the white blood cell count and numbness or tingling in the fingertips. In the study, the Abraxane was administered on a weekly schedule compared to injections every three weeks of Taxotere. "This is a win-win finding," Gradishar said. "The weekly schedule of Abraxane has more antitumor effects and is better tolerated than Taxotere. There is also evidence that Abraxane is able to deliver the chemotherapy drug more effectively to the tumor." The Phase II, open-label, randomized clinical study involved 300 patients with previously untreated metastatic Stage 4 breast cancer. The results were assessed by an independent radiology company and study investigators. The study was supported by Abraxis BioScience, which manufactures Abraxane. Gradishar is a member of the advisory boards for Abraxis and sanofi-aventis U.S., which manufactures Taxotere. He has received grant support from Abraxis and sanofi-aventis. Source: EurekAlert! 5/26/09

Researchers Find No Adjustment Method Fully Resolves Confounding by Indication

Researchers at Boston University School of Medicine (BUSM) and Boston University School of Public Health have found that no adjustment method fully resolves confounding by indication in observational studies, meaning when the validity of a study is threatened by unmeasured confounding, it is not straightforward to determine which method of adjustment, if any, is most effective in obtaining a valid and precise estimate of effect. The study appears online in the Journal of Clinical Epidemiology. According to researchers, conventional methods to adjust for confounding, such as restriction and multivariable regression, leave residual confounding because of unmeasured factors. Propensity scores (PS) and instrumental variable (IV) methods have become increasingly popular with the intent to address residual confounding by simulating a randomized environment. Using data from the Breast Cancer Effectiveness in Older Women study, a collaboration of investigators from the National Cancer Institute-funded Cancer Research Network, the researchers compared methods used to reduce confounding to estimate incidence rates of breast cancer recurrence in older women who received adjuvant chemotherapy compared to women who did not. The researchers examined women 65 years of age or older diagnosed with early stage breast cancer. For women classified as high risk for recurrence, 20 percent experienced a breast cancer recurrence. In the unrestricted cohort, receipt of adjuvant chemotherapy was associated with recurrence. The PS distributions among women who received chemotherapy among those who did not showed no substantial overlap. Using the IV method, recurrence yielded a protective estimate. However, imbalances of measured factors across levels of the IV suggested residual confounding. "With minimal trial-based information available to inform clinical guidelines, which currently offer no guidance for treating older women with cancer, nonrandomized studies are vitally important," said lead author Jaclyn Bosco, MPH, project director in the Section of Geriatrics at BUSM. "Nonrandomized studies are only reliable when confounding by indication is handled adequately. When treatment with adjuvant chemotherapy among older patients is based on clinical judgment, controlling for prognostic factors alone leaves residual confounding by indication." Researchers further stated that PS and IV analysis methods can be useful under specific situations, but neither method adequately controlled confounding by indication in this study. This study was funded by the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services. Source: EurekAlert! 5/26/09

Drug that Targets Vasculature Growth Attacks Aggressive Thyroid Cancer

A medication that helps stop the growth of new blood vessels has produced dramatic benefits for some patients with aggressive thyroid cancer, research from Mayo Clinic indicates. At the annual meeting of the American Society of Clinical Oncology, Mayo investigators reported that cancer in about two-thirds of 37 patients with aggressive differentiated thyroid cancer treated with the drug pazopanib either stopped growing, or quickly shrank. The patient responses seen to date are promising, the researchers say, because all patients had fast-growing cancers that had spread to their lungs, with half involving lymph nodes and 39 percent also involving bones. “The benefits were striking in many patients to a degree we have not previously seen in thyroid cancer in response to other therapies, including the standard treatment of radioiodine,” says Keith Bible, MD, PhD, a medical oncologist and researcher who led the multicenter clinical trial funded by the National Cancer Institute. Most of the patients treated were enrolled at the Mayo Clinic campuses in Minnesota and Florida. Approximately one-third of patients achieved sustained and dramatic benefit from pazopanib, while another one-third experienced stabilization of their cancer or some tumor shrinkage. The remaining one-third of patients did not benefit from the drug. What is not yet known is the drug’s effect on overall survival. Pazopanib is also being studied in advanced kidney, ovarian, and other cancers. The drug, administered in pill form, targets proteins involved in angiogenesis, the growth of new blood vessels that has a critical role in the growth and spread of tumors. Mayo investigators are also leading clinical trials to test pazopanib in two other thyroid cancer subtypes--medullary, which does not respond to radioiodine, and anaplastic, the most aggressive subtype. Dr. Bible says plans are also under way to test pazopanib in a larger controlled and randomized clinical trial of patients with advanced differentiated thyroid cancer. Source: Newswise 5/14/09

Popular Cancer Drug Linked to Often Fatal Brain Virus

The 57-year-old lawyer in New York had handily completed the crossword puzzle in the Saturday New York Times--the hardest of the week--for years. But one Saturday morning, suddenly he could not retrieve the words to fill in the squares. In Chicago, an 83-year-old woman began parroting the same phrases over and over. When her doctor asked her how she was, she replied, "I am fine. I am fine. I am fine." The symptoms of the New York lawyer and the Chicago woman could have been mistaken for early dementia, but an MRI brain scan and biopsy revealed something surprising: It looked like their brains had been eaten away. A brain biopsy and a spinal tap confirmed the diagnosis of a swiftly moving and often fatal viral brain infection called progressive multifocal leukoencephalitis (PML) that attacks the brain's white matter. Both had lymphoma and had been taking the popular cancer drug rituximab (brand name Rituxan) before they developed the brain infection. The two patients are part of a new study from the Northwestern University Feinberg School of Medicine RADAR project, led by Charles Bennett, MD, that links rituximab to PML. Rituximab is the most important and widely used cancer drug for lymphoma. It is also approved for treatment of rheumatoid arthritis and is widely used off-label to treat multiple sclerosis, lupus erythematosus, and autoimmune anemias. Bennett reports on 57 cases from 1997 to 2008 in which patients with anemia, rheumatoid arthritis, or lymphoma developed the fatal brain disease after taking rituximab. They died an average of two months after being diagnosed. The study was published in the May 14 issue of the journal Blood. It is not yet known how rituximab is connected to the brain virus and who may be at risk. Bennett's RADAR project (Research on Adverse Drug Events and Reports) is an international consortium of physicians that collaborate to identify adverse reactions to medications and devices. Source: EurekAlert! 5/18/09

Heating Heart with Catheter Better than Drugs for Common Heart Rhythm Disorder

Treating a common heart rhythm disorder by burning heart tissue with a catheter works dramatically better than drug treatments, a major international study has found. One year after undergoing a treatment called catheter ablation, 63 percent of patients with an irregular heartbeat called atrial fibrillation were free of any recurrent atrial arrhythmias or symptoms. By comparison, only 17 percent of those treated with drugs were arrhythmia-free. Results were so convincing the trial was halted early. The study included 167 patients at 19 centers, including 15 centers in the United States. Lead researcher Dr. David Wilber presented the results at Heart Rhythm 2009 meeting in Boston, Mass., in May. Wilber is director of the Cardiovascular Institute at Loyola University Stritch School of Medicine in Maywood, Ill. In the study, 106 patients with frequent episodes of atrial fibrillation were randomly assigned to undergo ablation and 61 similar patients were randomly assigned to receive drug therapy. All patients had experienced at least three episodes of atrial fibrillation during the previous six months and had failed at least one attempt to control the rhythm with drugs. The study was funded by Biosense Webster, which makes the ThermoCool catheter used in the trial. Wilber is a consultant to the company. The study was the largest to date to compare ablation to drug therapy for atrial fibrillation. Earlier studies involved single centers and smaller sample sizes, Wilber said. An additional study called CABANA is designed to determine whether ablation patients live longer than patients receiving medication. Researchers will follow about 3,000 patients for three years. Source: EurekAlert! 5/14/09

Ginger Quells Cancer Patients' Nausea from Chemotherapy

People with cancer can reduce postchemotherapy nausea by 40 percent by using ginger supplements, along with standard antivomiting drugs, before undergoing treatment, according to scientists at the University of Rochester Medical Center. About 70 percent of cancer patients who receive chemotherapy complain of nausea and vomiting. "There are effective drugs to control vomiting, but the nausea is often worse because it lingers," said lead author Julie L. Ryan, PhD, MPH, assistant professor of dermatology and radiation oncology at Rochester's James P. Wilmot Cancer Center. The research will be presented at the American Society of Clinical Oncology meeting on May 30 in Orlando, Fla. Ryan's research is the largest randomized study to demonstrate the effectiveness of ginger supplements to ease postchemotherapy nausea. Previous small studies have been inconsistent and never focused on taking the common spice before chemotherapy. The Phase II/III placebo-controlled, double-blind study included 644 cancer patients who would receive at least three chemotherapy treatments. They were divided into four arms that received placebos, 0.5 gram of ginger, 1 gram of ginger, or 1.5 grams of ginger along with antiemetics (antivomiting drugs such as Zofran®, Kytril®, Novaban®, and Anzemet®). Patients took the ginger supplements three days prior to chemotherapy and three days following treatment. Patients reported nausea levels at various times of day during following their chemotherapy and those who took the lower doses had a 40 percent reduction. Ginger is readily absorbed in the body and has long been considered a remedy for stomach aches. "By taking the ginger prior to chemotherapy treatment, the National Cancer Institute-funded study suggests its earlier absorption into the body may have anti-inflammatory properties," Ryan said. Source: EurekAlert! 5/14/09

Novel Therapy May Prove Effective in Treatment of 30 Percent of Cancers

A groundbreaking Canada-wide clinical trial led by Dr. Katherine Borden, at the Institute for Research in Immunology and Cancer of the Université de Montréal, has shown that a common antiviral drug, ribavirin, can be beneficial in the treatment of cancer patients. Published in the journal Blood, the study demonstrates that ribavirin suppresses the activities of the eIF4E gene in patients. This gene is dysregulated in 30 percent of cancers including breast, prostate, head and neck, colon, and stomach cancer. The study was a joint project between Borden's research group, which monitored molecular events in trial patients, and Dr. Sarit Assouline of the Segal Cancer Centre, Jewish General Hospital, who led the clinical part of the trial. The integration of these two teams made it possible to rapidly move from a research lab to patient tests. The study team targeted the gene by giving trial participants a mimic of its natural target, ribavirin. "Our results are the first to show that targeting eIF4E in humans is clinically beneficial," explains Dr. Borden. The trial studied patients with M4/M5 acute myeloid leukemia who had undergone several other failed treatments. "We had striking clinical improvements with even partial and complete remissions," indicated Assouline. The next challenge for this team is to overcome the resistance that develops over time to ribavirin. "Combination therapy with chemotherapeutic agents may enhance the efficacy of this treatment," explains Borden. "Trials in the near future are planned to overcome this, and we are looking forward to more complete remissions. We also hope to test whether ribavirin is as effective in the treatment of other cancers with dysregulated eIF4E. Our laboratory studies suggest this is likely." The study was made possible thanks to a $600,000 grant awarded to Borden by the Leukemia and Lymphoma Society. Source: EurekAlert! 5/13/09

Clinical Trials for Shingles Drug Take an Important Step Forward

A possible new antiviral drug designated FV-100, which could alleviate the suffering of millions of people with herpes zoster or shingles, has entered the second stage of clinical testing in patients. Developed and patented by scientists based at Cardiff University, a Phase II clinical trial with FV-100 has recently been initiated in America. Previous research has shown the drug to be up to 10,000 times more potent than existing treatments in early lab tests. The drug was discovered by a team in the Welsh School of Pharmacy and a virology group at the Rega Institute in Belgium, and is being further developed in collaboration with the U.S-based biopharmaceutical company, Inhibitex Inc. Shingles is caused by the same viral infection that causes chicken pox. It is estimated that around one in five people in the U.S., Europe, and Japan will be affected by the debilitating condition during their lifetime. It is generally characterised by skin lesions, blisters and rash, and acute pain, and in many cases, postherpetic neuralgia, which is a painful and often highly distressing condition resulting from nerve damage caused by the virus. Cardiff University's Professor of Medical Chemistry Chris McGuigan, who led the team which discovered the antiviral drug said, "We believe this drug has the potential to be the most powerful inhibitor ever discovered to treat shingles. We are incredibly excited at the prospect of FV-100 becoming commercially available in the future, and potentially being the first drug discovered in Cardiff University to make it to the marketplace." Inhibitex anticipates completing its first Phase II trial of FV-100 in the first half of 2010. Russell H. Plumb, president and chief executive officer of Inhibitex, Inc, said, "We have more than 20 U.S sites qualified to enroll patients, and plan to ultimately utilize a total of 50 to 60 sites in this trial. We believe this enthusiastic response from the clinical community reflects its recognition of the significant unmet medical needs of the increasing number of shingles patients." Source: EurekAlert! 5/11/09

"Deidentified" Electronic Medical Records Transformed Rapidly into Population Studies

Clinical research studies at Montefiore Medical Center used to take months, required a committee of physicians and data experts, and involved an elaborate research review process. Now, many of these studies are performed by a single clinician in a matter of minutes using "deidentified" patient electronic medical records (EMRs) and a breakthrough software called Clinical Looking Glass (CLG). “This remarkable software taps into the large pool of EMR data collected here over the past decade,” said Steven Safyer, MD, president and CEO of Montefiore. “While EMRs have the ability to improve quality and reduce costs for single patients, CLG interprets this data for entire patient populations so that we can rapidly check the collective effectiveness of patient safety measures, conduct clinical research, and even comply with federal regulations. We believe it offers a glimpse into how healthcare informatics is shaping the future of medicine.” More than 700 physicians at Montefiore have taken a three-hour training session to learn how to apply CLG, which has been used to measure the impact of Medicare regulations on rehabilitation patients, quantify the reduction in radiation exposure for emergency department patients, provide data for professional articles on embolisms and hospital-based physicians, and check on a public health threat. With clinicians conducting an impressive 2,800 CLG inquiries, or analytics, every month, CLG has become an integral part of the culture of healthcare delivery at Montefiore, the teaching hospital for Albert Einstein College of Medicine. Because all of the analyses can be run without identifying the names of the patients, exploratory questions can be undertaken while protecting privacy. “The goal of these analytics is to gather information and conduct studies that lead to better clinical decision-making,” said Eran Bellin, MD, vice president for clinical information technology research and development at Montefiore, who was instrumental in designing CLG. “The queries have provided the quantitative evidence for dozens of peer-review journal articles, presentations at professional meetings, institution-wide patient quality improvement initiatives, and programs that benefit entire populations.” CLG is also being used by the New York City Department of Health in research studies, and is being considered for use by the healthcare system of the U. S. Department of Defense. Source: Newswise 5/11/09

Adding Antiviral Improves Response, Halves Duration of Hepatitis C Treatment

The addition of the antiviral drug telaprevir to a standard treatment for hepatitis C can shorten the duration of therapy and increase the number of patients who can be cured of their disease, according to the results of study coordinated by investigators from the Duke Clinical Research Institute (DCRI). "Standard treatment for the most common type of hepatitis C is 48 weeks of a combination of two drugs, peginterferon alfa-2a and ribavirin, which cures less than half of patients and has significant side effects that make it very difficult for some patients to continue their treatment," said John McHutchison, MD, a hepatologist and gastroenterologist and researcher at the DCRI, and lead investigator on this study. "Our study found that by combining the standard therapy with the direct antiviral drug telaprevir, we could reduce the duration of treatment by 50 percent, to 24 weeks, and, at the same time, improve the cure rate by 50 percent." The researchers published their findings in the April 30 issue of the New England Journal of Medicine. The study was funded by Vertex Pharmaceuticals, the maker of the drug telaprevir, a protease inhibitor that works by blocking an enzyme that the hepatitis C virus needs in order to replicate itself. In a randomized, Phase IIb, double-blinded, 37-center study of telaprevir in combination with peginterferon alfa-2a and ribavirin, the researchers examined the responses of 250 patients on four trial arms. Other researchers involved in this study include Gregory Everson of the University of Colorado Health Science Center; Stuart Gordon of Henry Ford Hospital; Ira Jacobson of Weill Cornell Medical College; Mark Sulkowski of Johns Hopkins School of Medicine; and Robert Kauffman, Lindsay McNair, and John Alam of Vertex Pharmaceuticals. Source: EurekAlert! 4/29/09

Therapy Based on Magnetic Stimulation Shows Promise for Migraines

A new University of California, San Francisco (UCSF) study examining the mechanism of a novel therapy that uses magnetic pulses to treat chronic migraine sufferers showed the treatment to be a promising alternative to medication. The therapy is called transcranial magnetic stimulation, or TMS. Study findings were presented in April during the annual American Academy of Neurology scientific meeting in Seattle. In a previous randomized, controlled clinical study by Ohio State University Medical Center, TMS was used to treat patients who suffer from migraine with aura, a condition in which a variety of mostly visual sensations come before or accompany the pain of a migraine attack. The study showed that TMS treatment was superior to the placebo given to the control group. Patients were pain-free at follow-up intervals of two, 24, and 48 hours. In the new study, conducted in rats, UCSF researchers focused on understanding the mechanism of action of TMS therapy--how the treatment interacted with the brain to produce the pain-free outcomes of patients in the previous study. The UCSF research identified potential opportunities to enhance treatment strategies in patients. One example, the study team noted, was that factors such as time and peak intensity of stimulation may be important components in the brain's response to TMS. Additional study investigators were Philip R. Holland, PhD, UCSF; and Carol T. Schembri and Joe P. Fredrick, Neuralieve, Inc., Sunnyvale, Calif. The research was funded by Neuralieve, which provided the TMS technology for the study. Source: EurekAlert! 4/29/09

Cancer Institute to Study Radiation Technology for Head and Neck Cancer

The Oregon Health & Science University's Knight Cancer Institute will evaluate whether the state-of-the-art image-guidance system called Calypso® (Calypso Medical, Seattle, Wash.) is as effective in delivering highly precise radiation therapy to head and neck cancer patients as it has been in those with prostate cancer. The Calypso system relies on three electromagnetic transponders, or beacons, about the size of a grain of rice that are implanted in the prostate prior to beginning treatments. These transponders utilize electromagnetic fields that can be detected with submillimeter precision for accurate daily targeting of the prostate gland. Continuous monitoring of the patient and prostate motion is also possible, which allows for greater accuracy in delivering radiation therapy and limits exposure to surrounding healthy tissue. In this new Phase II clinical trial, the beacons will be implanted into a customized mouth guard fitted to the participant's upper teeth/jaw. With the mouth guard in place, the research team will test whether daily patient positioning can be improved using this system. They will be able to monitor the participant's movement in real time throughout the seven-week course of treatment. This has proved difficult in the past without exposing the patient to additional radiation. This new research is funded in part through a grant from the American Society of Clinical Oncology Cancer Foundation. Source: EurekAlert! 4/28/09

Antiaging Cosmetic Reduced Wrinkles in Clinical Trial

Scientists testing an over-the-counter cosmetic antiaging product have shown it can clinically reduce wrinkles and improve the appearance of skin damaged by everyday exposure to sunlight. Dermatologists at the University of Manchester carried out a clinical trial on 60 volunteers with typical signs of sun-damaged skin and found that the cosmetic, No7 Protect & Perfect Intense Beauty Serum, made by Boots, could improve some of these clinical features. The study, published online in the British Journal of Dermatology in April, showed that 70 percent of individuals using the product had significantly fewer wrinkles after 12 months of daily use, compared to volunteers using a placebo. The research team, headed by Professor of Dermatology Chris Griffiths, reported last year that the original No7 serum stimulated the production of fibrillin-1, a protein that promotes elasticity in the skin. For this latest, year-long study, the researchers first wanted to discover whether the new No7 serum also promoted fibrillin-1 production, as well as to test whether this would result in a reduction in wrinkles, as has been demonstrated with prescription retinoids. Source: EurekAlert! 4/28/09

Pioneering Academic Raises Millions for "Cell Bandage"

A company cofounded by Professor Anthony Hollander, an academic from the University of Bristol, has raised more than £1.6 million to fund trials, including the first human study, of a pioneering "cell bandage" technology, which aims to save thousands of patients from the type of knee surgery that currently leads to premature osteoarthritis. Hollander came to national prominence as part of the academic team that saved the life of Claudia Castillio, after developing the first tissue-engineered trachea (windpipe) using the patient's own stem cells. This fully functioning airway was transplanted into the patient and saved her life. Azellon is now developing the first commercially practical applications of that same fundamental technology to create cell bandages that can be transplanted into a damaged knee meniscus, helping to regenerate the joint, and saving the patient from future surgery and potentially debilitating osteoarthritis. Azellon will develop a cell bandage grown from the patient's own stem cells, and transplant it in the patient's knee joint within three weeks of extracting the stem cells from bone marrow. The technology is believed to be the world's first adult and autologous (patient's own) stem cell treatment of meniscal tears. Azellon has raised the money from a consortium of funders that includes the Wellcome Trust, the Technology Strategy Board, IP Group, the Wyvern Fund, Oxford Technology Management, and the Universities of Bristol and Bath. The money raised will be invested in three preclinical trials covering safety, biodistribution, and cell fate, which will be carried out by University College London. In 2010, Azellon will initiate a human pilot study in Bristol. Source: EurekAlert! 4/20/09

Grapefruit Juice Boosts Drug's Anticancer Effects

In a small, early clinical trial, researchers at the University of Chicago Medical Center have found that combining eight ounces of grapefruit juice with the drug rapamycin (sirolimus) can increase drug levels, allowing lower doses of the drug to be given. They also showed that the combination can be effective in treating various types of cancer. For two decades, pharmacists have pasted DO-NOT-TAKE-WITH-GRAPEFRUIT-JUICE stickers on various pill bottles, because it can interfere with the enzymes that break down and eliminate certain drugs. This interference makes the drugs more potent. In data presented at the American Association for Cancer Research 100th Annual Meeting 2009, the Chicago researchers examined ways to exploit this fruit's medication-altering properties. "Grapefruit juice can increase blood levels of certain drugs three to five times," said study director Ezra Cohen, MD, a cancer specialist at the medical center. "This has always been considered a hazard. We wanted to see if, and how much, it could amplify the availability, and perhaps the efficacy of rapamycin, a drug with promise for cancer treatment." This trial was designed to test "whether we could use this to boost rapamycin's bioavailability to the patient's advantage, to determine how much the juice altered drug levels, and to assess its impact on anticancer activity and side effects," he said. The study followed 28 patients with advanced solid tumors, for which there is no effective treatment. The dose of the drug increased with each group of five patients, from 15 milligrams up to 35. Patients took the drug by mouth, as a liquid, once a week. Beginning in week two, they washed it down with a glass of grapefruit juice (Citius paradisi), taken immediately after the rapamycin and then once a day for the rest of the week. Twenty-five participants remained in the study long enough to be evaluated. Seven of those 25 had stable disease, with little or no tumor growth. One patient had a partial response, with the tumor shrinking by about 30 percent. That patient is still doing well more than a year after beginning the trial. Less than 15 percent of rapamycin is absorbed when taken by mouth. This study showed that substances known a furanocoumarins, plentiful in some forms of grapefruit juice, can decrease the breakdown of rapamycin. This makes the drug reach higher levels in the bloodstream, two to four times the levels seen without a juice boost, and thus increases the amount of the drug that reaches its targets. Source: EurekAlert! 4/20/09

Targeted Agent Shows Promise in Biliary Cancer Study

An experimental agent has shown promising results in people with advanced biliary cancer, according to a multi-institutional clinical trial led by cancer researchers at the Ohio State University. The agent, known as AZD6244 (ARRY-142886), blocks certain enzymes that cancer cells need to proliferate and survive. The findings of the 28-patient, Phase II study were reported April 20 at the annual meeting of the American Association for Cancer Research in Denver, Col. The average progression-free survival achieved by patients in the study was one of the highest reported in the literature for this malignancy, with many patients gaining weight in a disease that is typically associated with significant weight loss. The drug, which is administered orally, seems to be well tolerated with mild toxicities. The agent belongs to a class of drugs called protein kinase inhibitors. This particular drug targets a protein kinase called MEK 1/2, which is part of a chemical pathway that is often damaged in many biliary cancer cases. In addition to Ohio State, study sites included the University of North Carolina, Vanderbilt University, and Emory University. By the trial's end, one patient had a complete response to the treatment (the tumor shrank until it was undetectable), two patients had partial tumor shrinkage, and 17 patients showed no further growth in tumor size; that is, they had stable disease that often was durable. A preliminary analysis of the study shows that patients experienced no cancer progression for 5.4 months on average, a time almost double what would typically be expected with therapy in biliary cancer. This is despite the fact that 40 percent of patients had one prior therapy before receiving AZD6244. A more final analysis of the study is under way. Patients who lacked a target protein called pERK did not seem to respond to the drug, suggesting that the drug may not work if the protein is missing in the cancer cells. Funding from the National Cancer Institute supported this research. Source: EurekAlert! 4/20/09

Gene Therapy for Muscular Dystrophy Shows Promise Beyond Safety

Researchers have cleared a safety hurdle in efforts to develop a gene therapy for a form of muscular dystrophy that disables patients by gradually weakening muscles near the hips and shoulders. Described as the first gene therapy trial in muscular dystrophy demonstrating promising findings, researchers from the University of Florida, Nationwide Children's Hospital in Columbus, Ohio, and the Ohio State University report how they safely transferred a gene to produce a protein necessary for healthy muscle fiber growth into three teenagers with limb-girdle muscular dystrophy. The findings, which have relevance to genetic disorders beyond muscular dystrophy as well as conditions in which muscles atrophy, were published online in the Annals of Neurology. "We think this is an important milestone in establishing the successful use of gene therapy in muscular dystrophy," said Jerry Mendell, MD, director of the Center for Gene Therapy in the Research Institute at Nationwide Children's Hospital and the lead author of the study. "This trial sets the stage for moving forward with treatment for this group of diseases, and we are very pleased with these promising initial results. In subsequent steps, we plan to deliver the gene through the circulation in hopes of reaching multiple muscles. We also want to extend the trials over longer time periods to be sure of the body's reaction." The trial evaluated the safety of a modified adeno-associated virus as a vector to deliver the alpha-SG gene to muscle tissue. "The safety data is accumulating because this is the same type of vector that we and other research groups have successfully used in gene therapy trials for other diseases," said Barry Byrne, MD, a University of Florida pediatric cardiologist who is a member of the university's Genetics Institute and director of the Powell Gene Therapy Center. "In this effort, although proof of safety was the main endpoint, the added benefit was that this was an effective gene transfer. Even though we were dealing with a small area of muscle, the effect was long-lasting, and that has never been observed before." "These exciting results demonstrate the feasibility of gene therapy to treat limb-girdle muscular dystrophy," added Jane Larkindale, portfolio director with Muscular Dystrophy Association Venture Philanthropy, a program that moves basic research into treatment development. "The lack of adverse events seen in this trial not only supports gene therapy for this disease, but it also supports such therapies for many other diseases." The research was supported by the Muscular Dystrophy Association and the National Institutes of Health. Source: EurekAlert! 4/15/09

Researchers Use Stroke Patient's Own Stem Cells in Trial

For the first time in the United States, a stroke patient has been intravenously injected with his own bone marrow stem cells as part of a research trial at the University of Texas Medical School at Houston. Roland "Bud" Henrich, 61, was transferred to Memorial Hermann–Texas Medical Center on March 25 after suffering a stroke while working on his farm in Liberty. He arrived too late to receive tissue plasminogen activator, the only treatment for ischemic strokes. He became the first patient in the trial. The Phase I safety trial, funded with a pilot grant from the National Institutes of Health and support from the Notsew Orm Sands Foundation, will enroll nine more patients who have suffered a stroke and can be treated with the stem cell procedure within 24 to 72 hours of initial symptoms. "It's still very early in this safety study, but this could be an exciting new therapeutic approach for people who have just suffered a stroke," said Sean Savitz, MD, assistant professor of neurology at the medical school and the study's lead investigator. "Animal studies have shown that when you administer stem cells after stroke, the cells enhance the healing. We know that stem cells have some kind of guidance system and migrate to the area of injury. They're not making new brain cells, but they may be enhancing the repair processes and reducing inflammatory damage." Savitz said animal studies have shown that the healing effects of stem cells can occur as early as a week, but cautioned it is too early to attribute Henrich's improvement to the stem cell treatment. "I'm hoping he will get better and it will be because of the cells, but it's just hope at this point," Savitz said. The stem cells were harvested from the bone marrow in the iliac crest of his leg, then separated and returned to Henrich several hours later. Because they are his own stem cells, rejection is not expected to be an issue. When he arrived at the hospital, Henrich could not speak and had significant weakness on his right side. When he was released after nearly two weeks of hospitalization and rehabilitation, he was able to walk and climb stairs unassisted, and said his first words. Source: EurekAlert! 4/15/09

Vaccine Shows Promise in Fighting Early-Stage Lung Cancer

An experimental vaccine that triggers the patient's immune system to identify and attack specific tumor cells is showing new promise for the treatment of early-stage lung cancer. Thoracic surgeons at Rush University Medical Center in Illinois are researching the vaccine, called MAGE-A3 Antigen-Specific Cancer Immunotherapeutic, which is designed to kill cancer cells without harming normal cells. The MAGRIT (MAGE-A3 as Adjuvant Non-Small Cell LunG Cancer Immunotherapy) study is a randomized, double-blind, and placebo-controlled trial that will enroll patients with MAGE A-3-positive, non-small-cell lung cancers. The experimental vaccine targets MAGE-A3, a protein expressed in certain cancer cells but not in normal cells. Thirty-five percent of non-small-cell lung cancers have this protein, which also is present in some melanomas and head and neck cancers. "The principle is that you can possibly teach a patient's immune system to eliminate cancer cells that express certain proteins such as the MAGE-A3 protein," said Dr. Anthony Kim, thoracic surgeon and principal investigator of the study at Rush. "In a trial of early-stage lung cancer patients whose tumors expressed MAGE-A3, preliminary results showed that the vaccination reduced the risk of recurrence and the need for repeat surgery." The vaccination may be a promising alternative treatment solution for lung cancer patients who may not be ideal candidates for chemotherapy. A total of 182 patients with non-small-cell lung cancers were included in the early phase of the study sponsored by GlaxoSmithKline, which is developing the vaccine therapy. After having surgery to remove the tumors, 122 patients were randomly assigned to treatment with the MAGE-A3-targeting vaccine and 60 patients received placebo vaccines. Source: EurekAlert! 4/6/09 

Novel Needle Could Cut Medical Complications

Each year, hundreds of thousands of people suffer medical complications from hypodermic needles that penetrate too far under their skin. A new device developed by MIT engineers and colleagues aims to prevent this from happening by keeping needles on target. The device, which is purely mechanical, is based on concepts borrowed from the oil industry. It involves a hollow, S-shaped needle containing a filament that acts as a guide wire. When a physician pushes the device against a tissue, he or she is actually applying force only to the filament, not the needle itself, thanks to a special clutch. When the filament, which moves through the tip of the needle, encounters resistance from a firm tissue, it begins to buckle within the S-shaped tube. Due to the combined buckling and interactions with the walls of the tube, the filament locks into place "and the needle and wire advance as a single unit," said Jeffrey Karp, an affiliate faculty member of the Harvard-MIT Division of Health Sciences and Technology and cocorresponding author of a recent paper on the work in the Proceedings of the National Academy of Sciences. The needle and wire proceed through the firm tissue, but once they reach the target cavity (for example, a blood vessel) there is no more resistance on the wire, and it quickly advances forward while the needle remains stationary. Because the needle is no longer moving, it cannot proceed past the cavity into the wrong tissue. Karp believes that the device could reach clinics within three to five years, pending further preclinical and clinical testing. The work was funded by the Deshpande Center for Technological Innovation at MIT and the Center for Integration of Medicine and Innovative Technology. Source: EurekAlert! 4/2/09 

Drug Commonly Used for Alcoholism, Drug Addiction, Curbs Urges of Compulsive Stealers

It appears that a drug commonly used to treat alcohol and drug addiction has a similar effect on the compulsive behavior of kleptomaniacs--it curbs their urge to steal--according to new research at the University of Minnesota. The Medical School's Department of Psychiatry conducted an eight-week, double-blind study of 25 men and women ages 17-75, who spent an average of at least one hour a week stealing. Those who took the drug naltrexone (mean dose of 117 mg/day) reported significantly greater decline in stealing behavior compared to those taking placebo. The research is published in the April 1 issue of the Journal of Biological Psychiatry. "It gets rid of that rush and desire," said Jon Grant, MD, JD, MPH, an associate professor of psychiatry and principal investigator of the study. "The difference in their behavior was significant, and these people were really troubled by their behavior." While the drug is not a cure for kleptomania, Grant said it offers hope to those who are suffering from the addiction. He also said the drug would most likely work best in combination with individual therapy. Naltrexone is approved by the Food and Drug Administration for use in alcohol and opiate dependence, but it also has been studied and proved successful in helping gambling addicts. The research was supported by a Career Development Award from the National Institute of Mental Health and the University of Minnesota Academic Health Center. Source: EurekAlert! 3/31/09 

Hospital is New Clinical Coordinating Center for International Trial of Sepsis Drug

The Ocean State Clinical Coordinating Center (OSCCC), a collaboration of the pulmonary/critical care and infectious diseases divisions of Rhode Island Hospital in Providence, R.I., will serve as the academic clinical coordinating center in tandem with the Hospital St. Luc CCC in Brussels, Belgium for an international Phase II study of a drug to treat severe sepsis, called CytoFab. The center has been awarded an $800,000 grant from AstraZeneca to coordinate the randomized, multicenter trial. Steven LaRosa, MD, an infectious diseases specialist and director of the center, will oversee the hospital's role in the study. The OSCCC specializes in designing and implementing clinical trials of novel agents, diagnostics, and devices to confront medical issues related to critical care, infectious diseases, and biological defense. LaRosa adds, "This will be the fourth multicenter trial that we have coordinated at the OSCCC since our inception in 2004. We previously completed the largest clinical trial in severe community-acquired pneumonia." Source: EurekAlert! 3/30/09 

University's Bench-to-Bedside Research: Promising Treatment in Clinical Trials

A new drug developed at the University of California, Davis to treat diabetes, hypertension, and inflammatory disorders has entered Phase II of human clinical trials to evaluate its efficacy. The compound, a soluble epoxide hydrolase enzyme inhibitor, is "a first-in-class drug which may treat a suite of major cardiovascular and metabolic diseases," said entomologist Bruce Hammock, who with University of California, Berkeley cell biologist Sarjeet Gill discovered the enzyme in 1969 while researching fundamental insect biology. "This is one of the few examples of basic research in an academic laboratory moving through target validation and compound optimization all the way to the clinic," he said. The enzyme is involved in the metabolism of arachidonic acid and is in the same arachidonic biochemical pathway where such common pharmaceuticals as aspirin and ibuprofen are active. The Phase IIa clinical trial is a double-blind, placebo-controlled study. Officials will enroll a total of 150 patients with impaired glucose tolerance, mild obesity, and mild-to-moderate hypertension. Each patient will receive 28 days of treatment. The AR9281 enzyme inhibitor will be studied for safety, tolerability, reduction of blood pressure, and various measures of glucose and lipid metabolism. Results are expected in the first quarter of 2010. Source: EurekAlert! 3/26/09 

New Center is First in Nation to Offer Clinical Trials in Gene Therapy for Retinoblastoma

Doctors and researchers from four Texas Medical Center institutions have joined together in the fight against retinoblastoma, a childhood cancer of the eye. The result of their collaboration is the Retinoblastoma Center of Houston, which includes experts from Texas Children’s Cancer Center, the Children’s Cancer Hospital at the University of Texas M. D. Anderson Cancer Center, the Methodist Hospital, and Baylor College of Medicine. Retinoblastoma affects about 350 infants and children in the United States each year, and is the most common malignant tumor of the eye in children. Retinoblastoma is often curable, but may result in the loss of the eye. The center will be the first of its kind in the southwest region of the United States, and is the only one in the nation using gene therapy in clinical trials to treat and potentially find a cure for retinoblastoma. Patients will also have access to a special form of radiation called proton therapy, which helps to spare the healthy tissue around tumor areas and minimize the risk of secondary cancers. In addition, genetic testing will be part of the center, an important element because retinoblastoma is often hereditary. Source: Newswire 3/25/09 

New Drug Agent Knocks Out Multiple Enzymes in Cancer Pathway

A team of 24 researchers from the U.S., Europe, Taiwan, and Japan led by University of Illinois scientists has engineered a new anticancer agent that is about 200 times more active in killing tumor cells than similar drugs used in recent clinical trials. The study appears in the Journal of the American Chemical Society. The new agent belongs to a class of drugs called bisphosphonates. These compounds were originally developed to treat osteoporosis and other bone diseases, but were recently found to also have potent anticancer and immune boosting properties. When used in combination with hormone therapy in a recent clinical trial, the bisphosphonate drug zoledronate significantly reduced the recurrence of breast cancer in premenopausal women with estrogen-receptor-positive breast cancer. Similar results were reported previously for hormone-refractory prostate cancer. However, zoledronate quickly binds to bone, reducing its efficacy in other tissues. "We're trying to develop bisphosphonates that will be very active but won't bind to the bone, because if they bind to the bone they're not going to go to breast, lung, or other tissues," said University of Illinois chemistry professor Eric Oldfield, who led the new study. Oldfield's team also wanted to design a compound that would inhibit multiple enzymes in the tumor cell survival pathway, rather than just one, an approach analogous to the use of multikinase inhibitors in cancer therapy. One new compound, called BPH-715, which proved to be especially potent in cell culture and killed tumor cells in mice, has a very low chemical affinity for bone and activates gamma delta T-cells to kill tumor cells. Source: EurekAlert! 3/25/09 

Treatment Developed at Canadian University Heads to Nation's First TB Vaccine Clinical Trial

McMaster University researchers are about to launch Canada's first tuberculosis (TB) vaccine clinical trial with a vaccine totally designed, manufactured, and tested within McMaster. "The exciting thing for McMaster is that this is translational research that has gone from the basic science where the vector has been designed here at McMaster, then manufactured here, [and with] preclinical studies done at McMaster," said Dr. Fiona Smaill, a professor of medicine and chair of the Department of Pathology and Molecular Medicine. Development of the vaccine for the landmark trial was led by Zhou Xing, a professor in the same department. The vaccine was manufactured in the Robert E. Fitzhenry Vector Laboratory of the Institute of Molecular Medicine and Health on campus, Canada's first university laboratory certified to provide vectors (delivery agents) for use in clinical trials in humans. The Phase I clinical trial, which has the approval of Health Canada, will begin to recruit 48 healthy volunteers between 18 and 55 years of age in mid-April. Over 12 to 18 months, researchers will evaluate the safety of the new vaccine (currently called AdAg85A vaccine) and assess blood samples from vaccinated healthy human volunteers to determine if the vaccine is generating a desired immune response. The trial will be conducted by a team of infectious disease physicians, vaccine manufacturing specialists, and immunologists at McMaster. Initial financial support for the trial has come from the Centre for Gene Therapeutics, led by Jack Gauldie, and the Michael G. DeGroote Institute for Infectious Disease Research, both at McMaster University. The launch of the TB vaccine trial is part of McMaster's focus on research into infectious diseases that now claim millions of lives worldwide, specifically TB and HIV, with a focus on malaria planned for the near future. Source: EurekAlert! 3/19/09 

Vaccine to Prevent Colon Cancer Being Tested in Patients

Researchers at the University of Pittsburgh School of Medicine in Pennsylvania have begun testing a vaccine that might be able to prevent colon cancer in people at high risk for developing the disease. If shown to be effective, it might spare patients the risk and inconvenience of repeated invasive surveillance tests, such as colonoscopy, that are now necessary to spot and remove precancerous polyps. In a novel approach for cancer prevention, the vaccine is directed against an abnormal variant of a self-made cell protein called MUC1, which is altered and produced in excess in advanced adenomas and cancer. Vaccines currently in use to prevent cancer work via a different mechanism, specifically by blocking infection with viruses that are linked with cancer. Stimulating an immune response against the MUC1 protein in precancerous growths may be able to draw the immune system's fire to attack and destroy the abnormal cells. MUC1 vaccines have been tested for safety and immunogenicity in patients with late-stage colon cancer and pancreatic cancer. About a dozen people have received the experimental vaccine so far, and the researchers intend to enroll another 50 or so into the study. Participants must be between 40 and 70 years old and have a history of developing adenomas that are deemed advanced, meaning they are greater than or equal to 1 centimeter in size, are typed as villous or tubulovillous, or contain severely dysplastic, or abnormal, cells. After an initial dose of vaccine, the participants will get shots again two and 10 weeks later. Blood samples will be drawn to measure immune response at those time points as well as 12 weeks, 28 weeks, and one year later. Source: EurekAlert! 3/19/09 

Scientists Test Device to Treat Chemotherapy-Related Nausea

Trials to test acupressure wrist bands as a drug-free alternative for chemotherapy-related nausea are to take place at the University of Liverpool in the United Kingdom. More than 75 percent of patients undergoing chemotherapy experience nausea, which can impact negatively on their quality of life. Acupressure wrist bands can reduce the symptoms of travel sickness by applying force to the Nei Kuan pressure point on each wrist. The national study of more than 700 patients, at nine National Health Service (NHS) cancer centers, will measure the cost and clinical effectiveness of acupressure wrist bands in reducing and controlling chemotherapy-related nausea. Led by Professor Mari Lloyd-Williams, from the university's Academic Palliative and Supportive Care Studies Group, the team will analyze a wide range of patients, diagnosed with different types of cancer and undergoing chemotherapy, in order to discover which patient groups would most benefit from the intervention. Patients rank nausea and vomiting among the most distressing side effects of chemotherapy. In some cases, poorly controlled symptoms can lead to patients choosing to stop potentially curative treatment. These symptoms can contribute towards a loss of social life, prevent people from working, and lead to anxiety and depression. The trial will be the first of its kind to run in the NHS, and is funded by the National Institute for Health Research Health Technology Assessment program. The research will be carried out in collaboration with the University of Manchester, Salford University, and the University of Plymouth. Source: EurekAlert! 3/19/09 

Naltrexone Can Help Heavy Social Drinkers Quit Smoking

Naltrexone, an opioid antagonist approved in 1994 by the U.S. Food and Drug Administration for alcohol-dependence (AD) treatment, can reduce relapse rates among AD patients. Research on naltrexone's effectiveness on nicotine dependence is less clear, although researchers believe it may be helpful for specific smoker subgroups. A new study has found that naltrexone can help non-AD smokers who drink heavily on a social basis. Results will be published in the June issue of Alcoholism: Clinical & Experimental Research. "This was a smoking cessation trial," explained Andrea C. King, a psychologist and associate professor in the department of psychiatry at the University of Chicago, and first author of the study. "We examined smokers who did not have any other current addiction--besides tobacco--or mental or medical disorders, which may have confounded the results. The range of alcohol drinking was from abstainer to heavy social drinker." King and her colleagues examined 78 study participants (43 men, 35 women) drawn from a larger study looking at the effectiveness of naltrexone on smoking cessation. Of the 78, 34 were randomly assigned to receive naltrexone; 44 received a placebo. Dosage at 25 mg daily began three days prior to the quit date, and then continued at 50 mg daily for eight weeks. Drinking and liver enzyme levels were monitored, and all participants received nicotine patches (to ease withdrawal symptoms) and behavioral counseling for up to four weeks following the quit date. "Naltrexone, at 50 mg oral daily, when added to counseling and patch, significantly decreased heavy drinking rates in smokers enrolled in smoking cessation," said King. "Persons with the heaviest drinking patterns appeared to benefit the most from naltrexone, in terms of alcohol and smoking outcomes; it also increased their quit rates more so than in lighter drinkers." King noted that that these results are likely based on the strong interconnections between drinking and smoking for many individuals. "If we do support these findings with a larger sample, then use of naltrexone could be expanded to drinkers-smokers who are trying to quit smoking," she said. Source: EurekAlert! 3/19/09 

Vaccine Against CMV Shows Promise in Clinical Trial

A new vaccine has the potential to be the first to prevent maternal and congenital cytomegalovirus (CMV) infection, according to a University of Alabama at Birmingham (UAB) study published in the March 19 edition of the New England Journal of Medicine. Each year in the U.S., nearly 30,000 babies are born with congenital CMV, the most common virus transmitted by a pregnant woman to her unborn child, and nearly 8,000 of these children suffer permanent hearing, cognitive, or motor impairments. Although the first vaccine trials for CMV took place nearly 30 years ago, an effective vaccine has remained elusive. "The most striking result from this study is that the vaccine showed efficacy in the mothers, and is the first to do so," said study lead author Robert Pass, MD, professor in the UAB Department of Pediatrics. Pass and his colleagues, in a Phase II clinical trial, looked at 441 CMV-negative women who received either the vaccine or a placebo within one year of giving birth. The trial evaluated an experimental vaccine made from a single CMV protein, glycoprotein B, which is known to induce an immune response. The vaccine, supplied by Sanofi Pasteur, included an experimental adjuvant, MF59, supplied by Novartis. Women who received the vaccine were significantly more likely to remain uninfected throughout the 42-month follow-up period than those who received the placebo. Eight percent of vaccine recipients eventually became infected with CMV, while 14 percent of placebo recipients acquired a CMV infection by the time of the interim analysis conducted once all participants had at least six-month follow-up after the last study vaccine dose. Pass said that while a larger Phase III trial is needed to confirm the efficacy of the vaccine, these results are very promising. The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, sponsored the trial. Source: EurekAlert! 3/18/09 

Trial Shows No Early Mortality Benefit from Annual Prostate Cancer Screening

The prostate cancer screening tests that have become an annual ritual for many men do not appear to reduce deaths from the disease among those with a limited life-expectancy, according to early results of a major U.S. study involving 75,000 men. Results released in March from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial show that six years of aggressive, annual screening for prostate cancer led to more diagnoses of prostate tumors, but not to fewer deaths from the disease. The study, led by researchers at Washington University School of Medicine in St. Louis and conducted at 10 sites, is online and in March 26 print edition of the New England Journal of Medicine. "The important message is that for men with a life expectancy of seven to 10 years or less, it is probably not necessary to be screened for prostate cancer," says study lead author and principal investigator Gerald Andriole, MD, chief urologic surgeon at the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital. But it's too soon, he added, to make broad screening recommendations for all men based on the study's initial findings. "So far, only a minority of men enrolled in the PLCO study have died, so it may be premature to make generalizations about the ultimate results of the trial," he says. "We don't have enough data yet about the youngest men in the study--those in their 50s--and it may be that over time, we will, in fact, see a benefit from screening." The PLCO trial began in 1992 with funding from the National Cancer Institute, and was designed to determine whether prostate cancer screening reduces deaths from the disease. The trial involved 76,693 men, who were randomly assigned to receive either annual PSA blood tests for six years and digital rectal exams for four years or routine care, which included physical checkups but no mandate for annual prostate cancer screening. The new report includes data for all participants seven years after they joined the trial and for 67 percent of participants 10 years after they joined the trial. Source: EurekAlert! 3/18/09 

Unique Nerve-Stimulation Device Proves Effective Against Epilepsy

In a just-completed clinical trial, a unique nerve-stimulation treatment for intractable epilepsy reduced the number of seizures by more than 50 percent. In the March edition of the journal Neurology, University of California, Los Angeles neurology professor Christopher M. DeGiorgio and colleagues report the results of a long-term pilot trial that demonstrated the effectiveness of the new treatment, called trigeminal nerve stimulation. The results, though preliminary, are very encouraging, DeGiorgio said. Those participating in the trial for three months saw a 66 percent reduction in the number of seizures, those participating for six months saw a 56 percent reduction, and those who completed one year saw a 59 percent reduction. One of the subjects who participated for a full year had a 90 percent reduction in seizures. The trigeminal nerve extends into the brain from the face and forehead and is known to play a role in seizure inhibition. The stimulator, about the size of a large cell phone, attaches to a belt or can slip into a pocket. Two wires from the stimulator are passed under the clothing and connected to electrodes attached to the forehead by adhesive. The electrodes, which can be covered by a cap or scarf, transmit an electrical current to the nerve. A larger clinical trial to further test for safety and effectiveness is now under way. The investigators hope that eventually a device can be permanently implanted above the eyebrow that would stimulate the trigeminal nerve and replace the external device. Funding for the research was provided by Advanced Bionics and Boston Scientific and by grants from James Peters and the Salter, Brill, Jacoby, Lagermeier, Lester, and Johnson families. The Epilepsy Research Foundation–Therapy Development Program and Boston Scientific fund the new study. Source: EurekAlert! 3/18/09

FDA and Institutions to Collaborate Under Nanotechnology Initiative

The U.S. Food and Drug Administration (FDA) in March unveiled a new collaborative initiative with the Houston-based Alliance for NanoHealth (ANH) and its eight member institutions to help speed development of safe and effective medical products in the emerging field of nanotechnology. Under a Memorandum of Understanding, the FDA/ANH Nanotechnology Initiative will work to expand knowledge of how nanoparticles behave and affect biologic systems, and to facilitate the development of tests and processes that might mitigate the risks associated with nanoengineered products. All outcomes from this public-private partnership will be placed in the public domain for the benefit of all stakeholders. The eight academic institutions include Baylor College of Medicine, the University of Texas' M.D. Anderson Cancer Center, Rice University, the University of Houston, the University of Texas Health Science Center at Houston, Texas A & M Health Science Center, the University of Texas Medical Branch at Galveston, and the Methodist Hospital Research Institute. Source: FDA News 3/10/09 

Scientists Advance Stem Cell Research

Scientists at the University of Texas Health Science Center at Houston are on the forefront of stem cell research, developing novel therapies designed to generate heart cells, repair traumatic lung injuries, grow new bone, and stanch the spread of cancer cells. In one example of adult stem cell research touted by the university, Yong-Jian Geng, MD, PhD, professor of medicine and director of the Center for Cardiovascular Biology and Atherosclerosis Research, and James Willerson, MD, professor and chair of internal medicine, are conducting a clinical trial on treating chronic heart failure with stem cells that is supported by the National Institutes of Health (NIH). Meanwhile, principal investigator Charles Cox, MD, professor of pediatric surgery, is leading a unique clinical trial that will gauge the safety and potential of treating children who have just suffered traumatic brain injury with stem cells derived from their own bone marrow. Approved by the Food and Drug Administration and the university's Committee for the Protection of Human Subjects, the clinical trial is building on animal-model research indicating that bone-marrow derived stem cells can migrate to an injured area of the brain and support brain repair. Ten patients were recruited between 2005 and 2008, and the study will be completed this summer. Sean Savitz, MD, assistant professor of neurology, has begun a similar Phase I safety study using bone marrow stem cells in acute stroke patients admitted to the emergency center at Memorial Hermann-Texas Medical Center. The study uses the patients’ own bone marrow and is funded with a $130,000 NIH pilot grant. Enrollment of 10 patients is under way. Source: Newswise 3/6/09 

Measuring the Impact of Electronic Medical Records

The push is on to bring the U. S. healthcare system into the digital age by replacing paper-based systems now used at many medical facilities with electronic medical records systems and other information technology tools. To understand how best to realize the benefits these systems can provide, a team of experts at Worcester Polytechnic Institute has launched a three-year study of health information technology (HIT) systems now in various stages of implementation at four medical organizations—two in the United States and one each in Canada and Israel. Funded by a $750,000 grant from the National Science Foundation, the study will focus on the primary care setting to examine and analyze how implementing HIT systems impacts medical providers, their patients, and the operations of the healthcare delivery system. The goal of the study is to develop new insights and best practices to help guide future HIT implementations at other medical facilities. "Adapting to computer systems will be a learning process for primary care organizations, for physicians, and even for patients," said Diane Strong, PhD, professor of management. "From what we observe, we will develop new ideas and new concepts for healthcare delivery, such as better ways of organizing work flow and decision making to take advantage of the new opportunities enabled by these IT systems." In the United States, the study will focus on two organizations in Massachusetts: Fallon Clinic, a large group medical practice located throughout Central Massachusetts, and UMass Memorial Heath Care, an integrated medical system with 700 primary care physicians, several community hospitals, and an academic medical center serving Central New England. In Canada, which has universal coverage and a single-payer funding system, the study will include primary care offices of the Vancouver Coastal Health District. In Israel, which has a hybrid healthcare delivery model with four health funds that provide medical care to the entire population, the study will examine primary care practices in two of the health funds. These four sites were chosen because of their diversity of operating models, management structures, financial systems, and cultural differences. Source: EurekAlert! 3/5/09 

One Drug May Help People Both Lay Down the Drink and Put Out the Cigarette

A popular smoking cessation drug dramatically reduced the amount a heavy drinker will consume, a new Yale School of Medicine study has found. Heavy-drinking smokers in a laboratory setting were much less likely to drink after taking the drug varenicline compared to those taking a placebo, according to a study published online in the journal Biological Psychiatry. The group taking varenicline, sold as a stop-smoking aid under the name Chantix, reported feeling fewer cravings for alcohol and less intoxicated when they did drink. They were also much more likely to remain abstinent after being offered drinks than those who received a placebo, the study found. Additionally, there were no adverse effects associated with combining varenicline with alcohol in the doses studied. When combined with low doses of alcohol, varenicline did not change blood pressure or heart rate, nor did it seem to induce nausea or dizziness. "We anticipate that the results of this preliminary study will trigger clinical trials of varenicline as a primary treatment for alcohol use disorders, and as a potential dual treatment for alcohol and tobacco use disorders," said Sherry McKee, associate professor of psychiatry and lead author of the study. The study was funded by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health. Source: EurekAlert! 3/2/09

School of Medicine Gets $1 Million to Endow Chair in Clinical Pharmacology

The Rosalinde and Arthur Gilbert Foundation has pledged $1 million to fund an endowed chair in clinical pharmacology at the David Geffen School of Medicine at University of California, Los Angeles (UCLA). Clinical pharmacology bridges the gap between laboratory science and the practice of medicine; its primary aims are to promote safe and effective pharmaceutical drug use in patients and to optimize the medical benefits and minimize the potential risks of prescription drugs in treating diseases that affect humankind. The clinical pharmacology program at UCLA studies issues related to drug interactions, the individual's response to drugs, and how different ethnicities metabolize drugs. The endowed chair will be an administrative chair held by the director of UCLA's Interdepartmental Clinical Pharmacology Training Program, currently Dr. Barbara A. Levey. The chair's focus will be to catalyze the crucial work of UCLA's current program by augmenting research in this emerging discipline while reinforcing the importance of clinical pharmacology education at the Geffen School of Medicine. Source: Newswise 2/26/09 

Magnetic Device Studied as Treatment for Heartburn and Acid Reflux

More than 20 million Americans suffer from gastroesophageal reflux disease (GERD), experienced by many as chronic heartburn. Medication offers short-term relief for some sufferers of this disease. For those seeking a nonprescription alternative, a magnetic device, currently being evaluated at University of California, San Diego Medical Center, may provide a long-term solution. The device, called the LINX Reflux Management System, is being studied as part of a U.S. and European multicenter clinical trial. Santiago Horgan, MD, director of minimally invasive surgery, is the site’s principal investigator. “The goal of this clinical trial is to correct a defect in the lower esophagus so that the body can function naturally without pain or discomfort,” said Horgan. During a minimally invasive surgical procedure, the device, made up of a series of magnetic beads, is secured around the bottom of the esophagus. Once in place, the magnetic attraction between the beads supports a valve to protect the esophagus from reflux, while still allowing it to open during swallowing or to release gas. Made of permanent rare earth magnets encased in titanium, the band is sized to fit each patient. “I decided to participate in this clinical trial surgery because it may be a permanent, structural way of addressing the problem,” said Gina Levine, age 43, who has suffered from GERD for more than 18 years. Levine and other sufferers of GERD experience daily symptoms of burning, gas, and throat irritation. Other symptoms include regurgitation, chest pain, hoarseness, wheezing, and chronic cough. The clinical trial, sponsored by device manufacturer Torax Medical, Inc. of Shoreview, Minn., will evaluate the safety and effectiveness of the device in up to 100 patients. Source: Newswise 2/23/09 

Clinical Trial Review Finds that Only Exercise Prevents Low-Back Problems

Low-back pain continues to impose a huge burden on industrialized societies in terms of symptoms, medical costs, productivity, and work absence. Annual costs related to back pain in the United States alone may run as high as $100 billion. However, a systematic review of the literature for high-quality scientific trials published in the February issue of The Spine Journal finds exercise in workplace and community settings effective in preventing new episodes of low-back problems. "Strong and consistent evidence finds many popular prevention methods to fail while exercise has a significant impact, both in terms of preventing symptoms and reducing back pain-related work loss," said Dr. Stanley J. Bigos, University of Washington professor emeritus of orthopaedic surgery and environmental health. Bigos and his colleagues assessed methodological quality and potential for bias of clinical trials in preventing episodes of back problems. The researchers found 20 controlled trials to be high-quality according to Cochrane Collaboration Back Review Group criteria. Seven of the eight trials promoting various exercise programs were found effective, but other common and popular methods failed, including reduced lifting programs, back or ergonomic educational interventions, lumbar supports, shoe inserts, and stress management. The new review does not, however, discredit popular ergonomic innovations that may increase productivity, product quality, and work comfort. "Ten years ago, some critics suggested we rely upon lower level studies. They maintained that it was not possible to perform high-quality clinical trials on preventive interventions for low-back problems in the workplace. However, our review demonstrates the viability of the growing number of high-quality trials providing more reliable evidence to guide back problem prevention efforts," said Bigos. Source: University of Washington press release 2/18/09 

University Launches Stem Cell Study for Acute Stroke Patients

A first-of-its-kind stem cell study to treat acute stroke victims is being launched by investigators at the University of Texas Medical School at Houston. The Phase I study, funded with a pilot grant from the National Institutes of Health, will use the patients' own stem cells. Researchers will enroll 10 patients who have just suffered a stroke and are being treated in the Emergency Center at Memorial Hermann – Texas Medical Center. Physicians will obtain permission from the patient or patient's surrogate. The stem cells will be harvested from the bone marrow in the iliac crest of the leg, then separated and returned to the patient within three to six hours. Because they are the patient's own stem cells, rejection is not expected to be an issue. The clinical study builds on laboratory and animal research indicating that stem cells from bone marrow can migrate to the injured area of the brain and help repair the damage. Source: EurekAlert! 2/13/09 

New Test May Help to Ensure that Dengue Vaccines Do No Harm

As vaccines against a virus that infects 100 million people annually reach late-stage clinical trials this year, researchers have developed a test to better predict whether a given vaccine candidate should protect patients from the infection or, in some cases, make it more dangerous, according to an article just published in the journal Clinical and Vaccine Immunology. Cases of tropical, mosquito-borne dengue fever have expanding globally for more than 50 years, with nearly a third of the human population in 100 countries now at risk of infection with the four types of dengue virus. Infection with the dengue flavivirus, which is related to West Nile Virus and Yellow Fever, results in an estimated 500,000 hospitalizations and 22,000 deaths, mostly among infants, each year, according to the World Health Organization. After decades of absence in the United States, experts say the disease is causing illness again along the Texas-Mexico border, and that widespread dengue infection in the continental United States is a real possibility. "Aggressive health education and mosquito abatement programs have saved lives, but hopes for a true solution lie with vaccine design," said Xia Jin, MD, PhD, associate professor in the Department of Medicine, Division of Infectious Diseases, at the University of Rochester Medical Center. "Our study shows that [our] new test is likely superior to the standard test in its ability to tell whether a patient's response to a vaccine is safe." A phenomenon called antibody-dependent enhancement has delayed the development of dengue vaccines for decades. The threat of enhancement dictates that any dengue vaccine must raise protective immunity against all four dengue serotypes simultaneously and equally, and several vaccine candidates have generated unequal responses across serotypes. That creates the possibility that some of the antibodies created by such vaccines could raise the risk for hemorrhagic fever and shock, and calls for the development of tests that can precisely measure enhancement risk. "With experimental vaccines from companies like GlaxoSmithKline and sanofi aventis entering Phase II and Phase III clinical trials this year, we hope the new test will be adopted widely and soon, because it is more likely to catch enhancement," Jin said. Source: EurekAlert! 2/12/09

World's First Cardiac Adult Stem Cell Trial to Take Place in Louisville

The world's first Phase I Food and Drug Administration-approved clinical trial using adult cardiac stem cells to treat heart disease will be conducted by a team of University of Louisville doctors at Jewish Hospital. For the first time, patients with advanced heart disease who already are undergoing bypass surgery will be recruited for participation in the clinical trial, which uses adult stem cells taken from the patient's own cardiac tissue. During surgery, a small piece of tissue that is routinely removed during the bypass procedure will be frozen and sent to Harvard University so that the adult cardiac stem cells can be extracted and removed. After the patient has recovered for three to four months, the cells will be directly injected into cardiac scar tissue using a minimally invasive cardiac catheterization procedure, which reaches the heart through a large artery in the patient's leg. The patients will be evaluated over the course of at least a year for heart function and blood flow. The heart's overall size and the size of the scar tissue will be measured. "Our hope is that the cardiac stem cells will help the heart tissue regenerate, reducing the size of the patient's scar tissue and improving heart function," said study leader Roberto Bolli, the Jewish Hospital Heart and Lung Institute Distinguished Chair in Cardiology. All patients enrolling in the clinical trial will receive the cardiac stem cell therapy, since this trial is designed to test the treatment's safety and feasibility. Source: PRNewswire 2/11/09

Clinical Trial Will Target Leading Cause of Autism in Girls

The Autism Consortium announced in February that several consortium members published a paper with significance for clinical trials in autism in the Proceedings of the National Academy of Sciences. The research, led by Mriganka Sur, PhD, the Newton Professor of Neuroscience at the Picower Institute and head of the MIT Department of Brain and Cognitive Sciences, and Rudolf Jaenisch, PhD, a founding member of the Whitehead Institute and professor of biology at MIT, demonstrates for the first time a mechanism for Rett Syndrome and a therapeutic that could be directly applicable to humans. As a result, a clinical trial in humans is in development. This groundbreaking study demonstrated that by treating mice with a peptide fragment of IGF1, a molecule that is utilized by the brain for neuronal and synaptic development, the symptoms of Rett Syndrome in the mice were largely reversed. "The next step is to test recombinant human IGF1, which is already available for pediatric use in humans with the hope of treating or reversing Rett Syndrome," said Omar Khwaja, MD, PhD, director of the Rett Syndrome Program at Children's Hospital Boston and head of the clinical trial team for IGF1. "We are working as quickly possible to develop the protocol, secure funding, and initiate the trial." Rett Syndrome, a neurodevelopmental disorder mainly affecting girls and also the most common basis of autism in girls, is primarily caused by a sporadic mutation in the MECP2 gene on the X chromosome. Source: EurekAlert! 2/9/09

Drug Discovery Short-Circuits Cancer Growth

A new drug that blocks cancer's main source of growth has been created in the lab and proven effective in mice, scientists are reporting. It is now being readied for clinical trials in patients. Far more potent than similar compounds already in clinical trials, the drug short-circuits the normal ability of cells to sense the need to grow and divide--a signal that cancer cells exploit to spread in the body. The scientists are working with clinicians to test the drug's effectiveness against a range of cancers that have proven difficult to treat. The discovery is reported in the February 10 edition of PLoS Biology. The research was led by scientists at the University of California, San Francisco (UCSF) and the UCSF Helen Diller Family Comprehensive Cancer Center. Senior author of the paper is Kevan Shokat, PhD, the Howard Hughes Medical Investigator and professor of cellular and molecular pharmacology at UCSF. Clinical trials are under way to stymie cancer proliferation by using a drug called rapamycin (marketed as Rapamune) or related compounds to block the growth signal cycle. The new drug greatly improves on rapamycin's effectiveness, the scientists reported. Of serious concern to clinicians, rapamycin and related drugs can actually promote cancer at the same time they thwart it. This happens, the scientists found, because the drugs only partially block the cells response to a growth signal. When this happens, the drugs end up augmenting the growth signal itself because a feedback process in the cell kicks in to assure adequate nutrition. With the feedback system in play, cancer cells can regain needed nutrients and continue to proliferate. The new drug totally blocks this feedback loop. The lead author on the PLoS Biology paper is Morris E. Feldman, a graduate student in Shokat's lab. Other coauthors come from UCSF and the University of Geneva. The research was funded by the Howard Hughes Medical Institute. Source: EurekAlert! 2/9/09

Teaching An Old Drug New Tricks

A century-old drug that failed in its original intent to treat tuberculosis, but has worked well as an antileprosy medicine, now holds new promise as a potential therapy for multiple sclerosis and other autoimmune diseases. "We never expected that an old antibiotic would hit this target that has been implicated in multiple sclerosis, psoriasis, and Type 1 diabetes," says Johns Hopkins pharmacologist Jun O. Liu. "People have been working for years and spending tens of millions of dollars on developing a drug to inhibit a specific molecular target involved in these diseases, and here we have a safe, known drug that hits that target," known as the Kv1.3 potassium channel. The finding about clofazimine, a synthetic compound made in the 1890s, is reported in PLoS One by researchers who uncovered the drug's latest potential during an ongoing and exhaustive screening of FDA-approved drugs designed to identify new uses for them. The team was specifically hunting for immune system control agents within the Johns Hopkins Drug Library, a collection assembled over the past seven years by Liu and colleagues of more than 3,000 drugs in pharmacies or being tested in Phase II clinical trials. The team first engineered cells to mimic an immune cell's natural signaling pathway, a complex and circuitous route from the cell surface to the genetic switch inside. They then subjected these specialized cells to the Drug Library, one at a time, and identified more than 200 hits--drugs that inhibited the signaling system by more than 50 percent. When they compared the potency of the 200 with each other, "clofazimine was the hit with the highest inhibitory activity," Liu says. In addition to Liu, authors of the PLoS One paper come from Johns Hopkins, the University of Hawaii, and Northwestern University. Source: EurekAlert! 1/30/09

$11 Million from NIH to Help University Coordinate Hepatitis Effort

The National Institute of Diabetes and Digestive and Kidney Diseases has awarded a seven-year, $11 million grant to the University of Pittsburgh Graduate School of Public Health to coordinate the Hepatitis B Clinical Research Network--a consortium of 15 clinical and research centers in the U.S. and Canada that will conduct translational research on hepatitis B. The network will include a multisite treatment trial, create and maintain a large database of study results, and store tissue and serum samples to facilitate clinical and basic research. "Medical advances have led to many treatments for chronic hepatitis B infection, and most patients respond to them," said Steven Belle, PhD, principal investigator of the data coordinating center and professor of epidemiology at the university. "However, these treatments do not cure the infection, but contain it by making it more difficult for the virus to reproduce." Many patients need to stay on therapy for a long time, and when treatment is prolonged, the virus can become resistant, making further treatment ineffective. "We don't know why treatment works better for some patients than others, and we cannot accurately predict who may go on to develop liver abnormalities," said Belle. "But with the interdisciplinary expertise within the network, we hope to learn more about the immune changes that occur with hepatitis B infection and make inroads to finding a lasting cure." The network also includes Harvard University; Johns Hopkins University; Mayo Clinic; Saint Louis University; University of California at Los Angeles; University of California, San Francisco; University of Michigan; University of North Carolina at Chapel Hill; University of Pennsylvania; University of Texas Southwest; University of Toronto; University of Washington; Virginia Commonwealth University; the Centers for Disease Control and Prevention; and the National Institutes of Health. Source: EurekAlert! 1/29/09

Stem Cell Transplant Reverses Early-Stage Multiple Sclerosis

Researchers from Northwestern University's Feinberg School of Medicine appear to have reversed the neurological dysfunction of early-stage multiple sclerosis (MS) patients by transplanting their own immune stem cells into their bodies and thereby "resetting" their immune systems. "This is the first time we have turned the tide on this disease," said principal investigator Richard Burt, MD, chief of immunotherapy for autoimmune diseases at the Feinberg School. The clinical trial was performed at Northwestern Memorial Hospital, where Burt holds the same title. The patients in the small Phase I/II trial continued to improve for up to 24 months after the transplantation procedure and then stabilized. They experienced improvements in areas in which they had been affected by MS, including walking, ataxia, limb strength, vision, and incontinence. The study was published online January 30 and will appear in the March issue of The Lancet Neurology. The 21 patients in the trial, ages 20 to 53, had relapsing-remitting MS that had not responded to at least six months of treatment with interferon beta. After an average follow-up of three years after transplantation, 17 patients (81 percent) improved by at least one point on a disability scale. The disease also stabilized in all patients. In the procedure, Burt and colleagues treated patients with chemotherapy to destroy their immune system. They then injected the patients with their own immune stem cells, obtained from the patients' blood before the chemotherapy, to create a new immune system. After the transplantation, the patient's new lymphocytes or immune cells are self-tolerant and do not attack the immune system. In previous studies, Burt had transplanted immune stem cells into late-stage MS patients. "It didn't help in the late stages, but when we treat them in the early stage, they get better and continue to get better," he said. "What we did is promising and exciting, but we need to prove it in a randomized trial." He has launched a randomized national trial. Source: EurekAlert! 1/29/09

Informatics Pilot Projects to Aid Clinical and Translational Scientists Nationwide

The National Institutes of Health (NIH) has awarded three contracts for pilot projects to improve informatics support for researchers conducting small- to medium-sized clinical studies. Each of the two-year contracts, which will total up to an estimated $4 million, represents a collaboration among individuals at three or more institutions that receive NIH Clinical and Translational Science Awards (CTSA). Administered by the National Center for Research Resources (NCRR), one of the CTSA program goals is to advance collaborations in clinical and translational research by interdisciplinary teams of investigators. These collaborations help enable the translation of rapidly evolving information developed in basic biomedical research into treatments and strategies to improve human health. Informatics support includes systems that store, process, and facilitate the exchange of information. The pilot projects will be led by Case Western Reserve University, Cleveland, Ohio; University of Washington, Seattle; and Vanderbilt University, Nashville, Tenn. "These projects, which will build on the existing strong informatics expertise at the institutions, will promote new ways in which to enable researchers to collaborate and communicate across the CTSA consortium and with other partners in their research," said NCRR Director Barbara M. Alving, MD. "The projects are one important part of a larger effort to achieve the potential of clinical and translational science and reduce the time it takes to develop new treatments for disease." Full project descriptions provided by each lead institution, as well as a list of project partner institutions, are available here. Software resulting from these pilot projects will be freely available to biomedical researchers, educators, and institutions in the nonprofit sector. The terms of availability will permit broad adoption of the tools and also allow for commercialization of enhanced or customized versions. The funding for these pilot projects is provided by the NIH Roadmap for Medical Research/Common Fund. Source: EurekAlert! 1/26/09

Drug-Coated Stents Less Risky than Bare-Metal Stents for Heart Bypass

Coronary bypass surgery may carry less risk of serious complications if stents coated with a drug that suppresses cell growth are used in the procedure rather than bare-metal stents, University of Texas Southwestern Medical Center researchers and colleagues have found. The study, appearing online and in an upcoming issue of The Journal of the American College of Cardiology, is the first large, multicenter trial comparing two types of commonly used stents. In the study, researchers examined 80 patients, roughly half of whom had saphenous vein grafts with paclitaxel-eluting stents and the other half who had the same procedure with bare-metal stents. Researchers found that 51 percent of patients with the bare-metal stent had renarrowing of the vein graft over several months compared to 9 percent of the drug-eluting stent group. In addition, 28 percent of patients who had a bare-metal stent required another procedure to treat the same blockage, while only 5 percent of patients who had the drug-eluting stent did. Some previous studies have indicated that patients receiving drug-eluting stents in saphenous vein grafts may not reduce the risk of renarrowing and may be associated with increased risk of death. In this study, the rates of death were similar in both study groups, although the study was not designed to detect differences in mortality. The researchers now hope to repeat the study in an expanded group of patients, which would provide important data to determine definitively the efficacy and safety of each kind of stent. The trial was funded by the Department of Veterans Affairs and by the Harris Methodist Foundation. Other institutions involved in the study include the Veteran Affairs North Texas Healthcare System; the University of Toledo; Central Arkansas Veterans Healthcare System; the University of Arkansas for Medical Sciences; Onassis Cardiac Surgery Center; Michael E. DeBakey Veterans Affairs Medical Center; Iowa City Veteran Affairs Medical Center; Wheaton Franciscan Medical Group; and the Geisinger Clinic. Source: Newswise 1/22/09

Can an Anti-Inflammatory Drug Treat Type 2 Diabetes?

Joslin Diabetes Center scientists are taking groundbreaking research on the role of inflammation in Type 2 diabetes to a new level with the launch of a national clinical trial to investigate whether salsalate, an anti-inflammatory drug used for years to manage arthritis pain, can reduce blood glucose levels in people with Type 2 diabetes. If successful, the trial could lead one day to an inexpensive way to treat this most common form of diabetes, which has been increasing at epidemic rates in recent years. About 560 adults with poorly controlled blood glucose levels are being sought to participate for one year in a clinical research study, referred to as Targeting Inflammation with Salsalate in Type 2 Diabetes (TINSAL-T2D). The study is being funded by the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health, and conducted at Joslin in Boston and at about 20 other medical institutions across the nation. Initial studies by the Joslin group showed that salsalate was effective to lower blood glucose when given for three months, leading to the start of this larger trial of longer duration. For the TINSAL-T2D study, the researchers are seeking adults ages 18 to 75 whose glucose levels are not in good control and who do not take insulin. Participants must be using no medication or be taking only one or two oral medications, among other criteria. Most participants can expect their involvement to last about one year. Source: EurekAlert! 1/21/09

Experimental Therapy Turns On Tumor Suppressor Gene in Cancer Cells

Researchers at Mayo Clinic have found that the experimental drug they are testing to treat a deadly form of thyroid cancer turns on a powerful tumor suppressor capable of halting cell growth. Few other cancer drugs have this property, they say. In the February 15 issue of Cancer Research (available online January 20), they report that Daiichi Sankyo Co.'s RS5444, being tested in a Phase I/II clinical trial to treat anaplastic thyroid cancer, might be useful for treating other cancers. The agent is also known as CS-7017. From previous research, the investigators knew that RS5444 binds to a protein known as PPAR-gamma, a transcriptional factor that increases the expression of many genes. They had found that human anaplastic thyroid tumor cells treated with RS5444 expressed a protein known as p21, which inhibited cell replication and tumor growth, but they did not understand how. They have now discovered that the agent actually forces PPAR-gamma to turn on the RhoB tumor suppressor gene, which in turn induces p21 expression. The encouraging findings in preclinical studies led to the launch of a multicenter trial, testing use of RS5444 and paclitaxel chemotherapy in patients with thyroid cancer. The study is being conducted at Mayo Clinic campuses in Jacksonville, Fla. and Rochester, Minn. and at eight other sites nationally. The earlier study was funded by grants from the National Institutes of Health, Mayo Clinic Research Committee, the Florida Department of Health Bankhead Coley grant, and a grant for Rare Cancers from Dr. Ellis and Dona Brunton. Funding from Daiichi Sankyo is being used to conduct the clinical trial. Source: EurekAlert! 1/20/09

Depressed Adolescents Not Harmed by Being Part of Placebo Group

In a national clinical trial, adolescents with moderate-to-severe depression first given a placebo treatment and then an antidepressant medication alone or in combination with therapy responded just as well over the long term as participants who received active treatment throughout the study, University of Texas Southwestern Medical Center researchers report. Researchers found that at the end of nine months, children and teenagers first given placebo treatment for 12 weeks and then given active treatment had a response rate of 82 percent, compared to an 83 percent response rate for participants who received active treatment for the entire period. The study, available January 15 in the online advance edition of The American Journal of Psychiatry, is the first to address whether delaying effective treatment for adolescents assigned to initial treatment with a placebo group is ethical in research, said Dr. Betsy Kennard, associate professor of psychiatry and lead author of the study. "We don't want to put children and teenagers in any treatment that's harmful, and this shows that these adolescents were well cared for and went on to do just as well as the teens who initially received active treatments," Dr. Kennard said. "Without placebo groups, it's difficult to determine the efficacy of a treatment. Now we've shown scientifically that these trials are safe and effective. We do well by these kids. ...So it's OK to consider participating in research, even in a controlled study, because in a well-conducted trial, you receive a considerable amount of clinical care, and there is quite a bit of oversight." Researchers from Duke University Medical Center, Carolinas Medical Center, Case Western Reserve University, Children's Hospital of Philadelphia, Columbia University, Johns Hopkins University, University of Nebraska, New York University, University of Chicago/Northwestern University, Cincinnati Children's Hospital Medical Center, University of Oregon, and Wayne State University also participated in this research. The study was funded by the National Institute of Mental Health. Source: Newswise 1/15/09

New Drug Holds Out Promise of Normal Diet for Sufferers of Genetic Disease

Imagine being forced to say no to a child crying for more food at supper. That is normal life at the dinner table for parents with kids who suffer from phenylketonuria (PKU), a genetic disease that means the body cannot tolerate anything more than a low-protein diet. PKU is described by scientists as an autosomal recessive genetic disease that is characterized by a deficiency in an enzyme called phenylalanine hydroxylase (PAH). Without PAH, the body cannot metabolize the amino acid phenylalanine. It then builds up in the blood, crosses the blood-brain barrier, and causes severe brain damage. From infancy, PKU sufferers are restricted to a low-protein diet to avoid the worst complications of the condition. This diet is essential during childhood to prevent damage to the brain while it is still growing; however, it is now also recommended for life to optimize school performance, concentration, and the ability to think clearly. However, help may now be on the way. A new pharmaceutical being developed by researchers at McGill University and the McGill University Health Centre (MUHC), along with colleagues at the Scripps Research Institute and BioMarin Pharmaceutical Inc., is offering PKU sufferers the hope of being able to eat a normal, protein-rich diet. Their preclinical evaluation study was published in December in the Proceedings of the National Academy of Sciences. "As we go into clinical trials, we'll see how it works in humans," said study first-author Dr. Christineh Sarkissian, a research associate at McGill's Departments of Biology and Human Genetics and the MUHC/Montreal Children's Hospital Research Institute. "Certainly in the animal models we showed that the phenylalanine levels came down to normal. The treatment itself is enzyme therapy, so patients will receive an injection once or twice a week instead of, we hope, needing to be on the diet." Source: EurekAlert! 1/14/09

University Announces Partnership with Company for Schizophrenia Drug Research

Vanderbilt University in January announced a licensing and research agreement with Janssen Pharmaceutica N.V., focusing on discovery of novel drugs for the treatment of schizophrenia. Under the terms of the agreement, Vanderbilt grants the company a worldwide exclusive license to existing compounds acting on a neurotransmitter receptor target, and provides a mechanism for the discovery and licensing of additional novel compounds over the next three years. The agreement provides for a total of $10 million in upfront payment and committed research funding to the laboratory of Jeffrey Conn, PhD, director of Vanderbilt’s Program in Drug Discovery. Additional payments will be made based on meeting certain milestones and through royalties on product sales. Vanderbilt will use its drug discovery infrastructure, including high throughput screening, medicinal chemistry, molecular biology, and pharmacology testing, to create novel compounds with properties compatible with becoming schizophrenia drugs. In addition to carrying selected compounds from the collaboration into clinical development and through commercialization, Janssen Pharmaceutica N.V. will bring its expertise to the partnership through input on compound design, synthesis, and later-stage safety and pharmacokinetic studies. Source: Newswise 1/9/09 

Novel Prostate Cancer Vaccine Aims for Cancer Cell "Sweet Spot"

Molecules of sugar sitting on the surface of cancer cells are keys to the development of a new vaccine aimed at both treating and stopping the spread of certain types of cancers called carcinomas, which include prostate, breast, ovarian, and lung, among others. Armed with a new two-year grant for $600,000 from the Gateway for Cancer Research, an Illinois-based philanthropic foundation, immunologist Alessandra Franco, MD, PhD, and her coworkers at the Moores Cancer Center at the University of California, San Diego are hoping to develop a low-cost immunotherapy for prostate carcinoma that may also have use against a variety of other carcinomas. The researchers have designed "glycopeptides," compounds in which sugars are linked to peptides that are recognized by T-cells. When given as part of a vaccine therapy, these glycopeptides rouse immune system T-cells into recognizing TACA on tumor cell surfaces, attacking and killing the cancer cells. Studies in the first year of the grant are focusing on gathering further laboratory and preclinical data to show the vaccine's effectiveness. Franco is hoping to begin a clinical trial in the second year of the grant to test the vaccine on prostate cancer patients who have already had treatment but who are at extremely high risk for relapse. Source: EurekAlert! 1/8/09 

New Drug May be Treatment Option for Fragile X Syndrome

A pilot trial of an oral drug therapy called fenobam has shown promising initial results and could be a potential new treatment option for adult patients with Fragile X syndrome (FXS). Findings of the open label, single-dose study by researchers at Rush University Medical Center and the University of California, Davis Medical Center are to be published in the January issue of the Journal of Medical Genetics. Results of an initial evaluation of the safety of fenobam, which is an mGluR5 antagonist, in adult males and females with FXS showed there were no adverse side effects from the medication. Dr. Elizabeth Berry-Kravis, pediatric neurologist at Rush, is principal investigator of the study. FXS is the most common inherited cause of mental impairment and the most common known cause of autism; symptoms include mental impairment, such as learning disabilities, attention deficit, hyperactivity, autistic-like behaviors, and anxiety and unstable mood. In the current study, 12 participants recruited by the researchers received a single oral dose of 50-to-150 mg of fenobam. Prepulse inhibition and continuous performance test were obtained before and after dosing to explore the effects of fenobam on measures of sensory gating, attention, and inhibition. In six of the 12 individuals, there was a 20 percent improvement. Source: EurekAlert! 1/7/09 

Hospital Joins Multicenter Study of Transplantation Option for Blood Malignancies

Children's Memorial Hospital in Chicago and the Gamida Cell-Teva Pharmaceutical Industries Joint Venture in January announced that Children's Memorial has joined a select group of cancer centers in Europe, the United States, and Israel that are actively enrolling patients for the ExCell study. The pivotal registration study is testing the safety and efficacy of the joint venture's StemEx® as a transplantation option for adolescents and adults with leukemia, lymphoma, and other high-risk hematological malignancies who are unable to find an adequately matched bone marrow donor. StemEx is a graft of expanded stem/progenitor cells, derived from a single unit of umbilical cord blood and transplanted in combination with nonexpanded cells from the same unit. While such blood has been used mainly for the treatment of small children, the increase in stem/progenitor cells through StemEx boosts the therapeutic potential of this treatment for adolescents and adults. Source: EurekAlert! 1/7/09 

Deep Brain Stimulation Results Mixed for Patients with Advanced Parkinson's Disease

Patients with advanced Parkinson disease who received deep brain stimulation treatment had more improvement in movement skills and quality of life after six months than patients who received other medical therapy, but also had a higher risk of a serious adverse events, according to a study in the January 7 issue of the Journal of the American Medical Association. "[R]ecent reports highlighting unexpected behavioral effects of stimulation suggest that deep brain stimulation, while improving motor function, may have other less desirable consequences," the authors write. They add that there are few randomized trials comparing treatments, and most studies exclude older patients. Frances M. Weaver, PhD, of Hines VA Hospital, Hines, Ill., and colleagues conducted a randomized trial to compare the benefits and risks of deep brain stimulation with those of best medical therapy for patients of a wide age range. A total of 255 patients were enrolled; 25 percent were age 70 years or older. The participants were randomized to receive bilateral deep brain stimulation with leads of the stimulation device implanted either in the subthalamic nucleus (60) or globus pallidus (61), or to receive best medical therapy (134). The researchers found that at six months, deep brain stimulation patients gained an average of 4.6 hours per day of good symptom control or unimpeded motor function without troubling involuntary movements, while the average change for the best medical therapy group was 0 hours. The overall risk of experiencing a serious adverse event was 3.8 times higher in deep brain stimulation patients than in best medical therapy patients. Source: EurekAlert! 1/6/09