Campus Connections

A Safer Alternative to Aspirin?

A study in China has shown that the antiplatelet drug cilostazol is as effective as aspirin at preventing recurrent stroke, but causes fewer bleeding events. The results suggest cilostazol could be a safer alternative to aspirin post-stroke for Chinese patients, and warrant both Phase III trials and studies in other populations. These are the conclusions of the authors of an article published early online and in the June edition of The Lancet Neurology. Aspirin is effective for preventing secondary stroke, and has been used in up to 89 percent of stroke patients. However, Asian populations are at higher risk of brain bleeding from aspirin use than other populations, and the incidence of such bleeding is higher in China than in high-income countries. Cilostazol is an alternative antiplatelet drug to aspirin that works through a different mechanism, and Dr. Yining Huang, Department of Neurology, Peking University First Hospital, Beijing, China, and colleagues conducted a randomized trial to compare the efficacy and safety of the two drugs at preventing recurrent stroke. Patients with a mean age of just over 60 years were enrolled, with 360 randomized to receive cilostazol and 359 to receive aspirin. Patients in both groups took the medication for 12 to 18 months, with the endpoint measured being any recurrence of stroke. The researchers found that 12 patients in the cilostazol group had a recurrence of stroke, compared to 20 in the aspirin group—translating to a 38 percent reduction in risk in the cilostazol group. These findings were not statistically significant, and thus can only be described as a trend. However, brain bleeding events were also much lower in the cilostazol group (one patient) versus the aspirin group (seven patients), and this was statistically significant. Source: EurekAlert! 5/4/08

Gene Therapy Improves Vision in Patients with Congenital Retinal Disease

In a clinical trial at the Children’s Hospital of Philadelphia, researchers from The University of Pennsylvania have used gene therapy to safely restore vision in three young adults with Leber congenital amaurosis (LCA), a rare form of congenital blindness. Although the patients have not achieved normal eyesight, the preliminary results set the stage for further studies of an innovative treatment for this and possibly other retinal diseases. An international team that also included members from the Second University of Naples and the Telethon Institute of Genetics and Medicine (both in Italy) and several other American institutions reported its findings in April in an online article in the New England Journal of Medicine. “This is the first gene therapy trial for a nonlethal pediatric condition,” said Albert M. Maguire, MD, an associate professor in Department of Ophthalmology at the University of Pennsylvania School of Medicine and a physician at the Children’s Hospital of Philadelphia. “Patients’ vision improved from detecting hand movements to reading lines on an eye chart.” The scientists used a vector, a genetically engineered adeno-associated virus, to carry a normal version of the gene, called RPE65, that is mutated in one form of LCA. Three patients received the gene therapy via a surgical procedure performed by Maguire between October 2007 and January 2008 at the Children’s Hospital of Philadelphia, where the gene vector was manufactured at the hospital’s Center for Cellular and Molecular Therapeutics. Starting two weeks after the injections, all three patients reported improved vision in the injected eye. Source: EurekAlert! 4/27/08

Cancer Researchers Receive Grant to Advance Brain Tumor Therapies

Cancer researchers at Children’s Hospital of Pittsburgh (part of the University of Pittsburgh Medical Center) and the University of Pittsburgh Cancer Institute (UPCI) will further develop novel treatments for brain tumors through a new, five-year, $6.24 million grant to the University of Pittsburgh School of Medicine. The grant from the National Institute of Neurological Disorders and Stroke will fund three projects aimed at developing cutting-edge treatment strategies for a type of brain tumor known as gliomas. The projects are led by principal investigator Ian Pollack, MD, chief of the Division of Pediatric Neurosurgery at Children’s Hospital and director of the UPCI Brain Tumor Program. “In the laboratory over the last five years, our researchers have developed three unique and promising approaches to treating gliomas, which are the most common form of brain tumors,” Dr. Pollack said. “Over the next five years, our goal is to take these approaches from the laboratory to clinical trial and begin to have a direct impact on patients diagnosed with brain tumors.” Source: EurekAlert! 4/24/08

A Simplified Method of Giving Rabies Vaccine

A clinical trial in healthy volunteers has found that a simpler and cheaper way of using rabies vaccines proved to be just as effective as the current, most widely used, method at stimulating antibodies against rabies. The trial is published in PLoS Neglected Tropical Diseases. Dr. Mary Warrell (Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, United Kingdom) and colleagues, who conducted the trial with a vaccine in routine use, say that the simplified method has the advantages of requiring fewer clinic visits, being more practicable and acceptable, and having a wider margin of safety, especially in inexperienced hands. The simplified regimen involves injections at four sites on the first day of treatment. The researchers vaccinated healthy volunteers to compare the antibody levels induced by the four-site intradermal regimen with those induced by the current two-site and eight-site intradermal regimens and the "gold standard" intramuscular regimen favored internationally. All of the economical intradermal regimens worked just as well as the intramuscular method at stimulating antirabies antibodies. Source: EurekAlert! 4/22/08

Scientists Test Device to Track Medication Adherence

A breath monitoring device developed by scientists at the University of Florida and Xhale Inc. could help prevent the emergence of drug-resistant strains of HIV and other infectious diseases by monitoring medication adherence in high-risk individuals. The device, which is slightly smaller than a shoebox, records the results of breath tests after patients should have taken medications that have been tagged with small amounts of an alcohol. The patients could then take a memory card or USB key to the clinic once a month and receive a printout of their results. In a test of the device, six healthy volunteers swallowed empty pills in which the capsules contained trace amounts of the alcohol. After five to 10 minutes, the scientists could measure the volatile byproduct in the volunteers’ breath using the detector. If patients don’t come after a certain amount of time, the machine can call the clinical trial coordinator and indicate that they did not take the medication as prescribed.  Source: EurekAlert! 4/21/08

Early Clinical Trial Results Back New Drug for Melanoma

Rutgers Professor Suzie Chen has found that riluzole, a drug already approved by the U.S. Food and Drug Administration (FDA) to treat Lou Gehrig’s disease (ALS), slows the growth of melanoma, the most aggressive form of malignant skin cancer. A Phase 0 (zero) clinical trial of riluzole (Rilutek), conducted by James Goydos, a surgical oncologist with the Cancer Institute of New Jersey, is in process with a small group of late-stage (stage 3 or 4) melanoma patients. Phase 0 is a recent designation by the FDA for exploratory, first-in-human trials. A grant from the National Cancer Institute enabled Goydos to begin the Phase 0 trial. Goydos and his colleagues recruited 11 patients to whom riluzole was administered for two weeks. “Our preliminary results show three solid positive responses in nine of the patients who had been able to complete the trial to date,” Goydos said. The next step is a combined Phase I/II trial that should begin in August with between 50 and 100 patients with stage 4 melanoma. Source: EurekAlert! 4/15/08

Stem Cell Research Leads to Clinical Trials for New Therapy

A unique partnership between industry and academia has led to human clinical trials of a new drug for a rare class of blood diseases called myeloproliferative disorders, which are all driven by the same genetic mutation and can evolve into leukemia. In just one year, collaborative discoveries by stem cell researchers from the University of California, San Diego (UCSD), Dana-Farber Cancer Institute, the Mayo Clinic, and a San Diego pharmaceutical company, TargeGen, moved from identification of the most promising drug candidate to clinical trials for the drug. A mouse model study headed by Catriona H.M. Jamieson, MD, PhD, assistant professor of medicine at UCSD, found an inhibitor that can stop the overproliferation of blood cells that results in problems with blood clotting, heart attacks and, in some cases, leukemia. Funded in part by a grant from the California Institute for Regenerative Medicine, the study was published in Cancer Cell on April 8. The drug is currently being tested in human clinical trials at the UCSD School of Medicine, the Mayo Clinic, M.D. Anderson Cancer Center, and the University of Michigan, Stanford, and Harvard University Schools of Medicine. Source: Newswise 4/7/08

Nanotechnology has Super-Sized Effect on Tumors

Anyone facing chemotherapy would welcome an advance promising to dramatically reduce their dose of these often harsh drugs. Using nanotechnology, researchers at Washington University School of Medicine in St. Louis have taken a step closer to that goal. The researchers used drug-coated nanoparticles to focus a powerful drug directly on tumors in rabbits. They found that a drug dose 1,000 times lower than used previously for this purpose markedly slowed tumor growth. The nanoparticles are extremely tiny beads of an inert, oily compound that can be coated with a wide variety of active substances. In an article published online in The FASEB Journal, the researchers describe a significant reduction of tumor growth in rabbits that were treated with nanoparticles coated with a fungal toxin called fumagillin. Human clinical trials have shown that fumagillin can be an effective cancer treatment in combination with other anticancer drugs. In addition to fumagillin, the nanoparticles' surfaces held molecules designed to stick to proteins found primarily on the cells of growing blood vessels. So the nanoparticles latched on to sites of blood vessel proliferation and released their fumagillin load into blood vessel cells. Fumagillin blocks multiplication of blood vessel cells, so it inhibited tumors from expanding their blood supply and slowed their growth. Human trials have also shown that fumagillin can have neurotoxic side effects at the high doses required when given by standard methods. But the fumagillin nanoparticles were effective in very low doses because they concentrate where tumors create new blood vessels. The rabbits that received fumagillin nanoparticles showed no adverse side effects. The nanoparticles measure only about 200 nanometers across, or 500 times smaller than the width of a human hair. Their cores are composed mostly of perfluorocarbon, a safe compound used in artificial blood. The nanoparticles can be adapted to many different medical applications. In addition to carrying drugs to targeted locations, they can be manufactured to highlight specific targets in magnetic resonance imaging, nuclear imaging, CT scanning, and ultrasound imaging. The researchers say they believe nanoparticle technology will be very useful for monitoring cancer treatment results in both the short and long term. The nanoparticles will be tested this year in preliminary human clinical trials to determine the optimal method for using them as imaging agents. These studies will lay essential groundwork for using the nanoparticles as therapeutic agents. Source: EurekAlert! 4/2/08

Clinical Trial that May Help Patients Breathe Easier Begins

Researchers at Suburban Lung Associates and the Chicago Chest Center recently announced the start of the EASE (Exhale Airway Stents for Emphysema) trial to explore an investigational treatment for advanced widespread emphysema. The trial focuses on airway bypass, a minimally invasive bronchoscopic procedure designed to help patients with emphysema/COPD (chronic obstructive pulmonary disease) breathe more easily. Central DuPage Hospital is the only site for the EASE trial in the Chicago area. “Airway bypass could be groundbreaking because it is a potential nonsurgical treatment for the patient with diffuse emphysema,” states Dr. Kevin Kovitz, interventional pulmonologist and principal investigator of the study at the Central DuPage Hospital site. “Emphysema, which permanently destroys lung function, is such a devastating disease, and any potential new treatment option could offer substantial relief to the millions who struggle with each breath.” During the airway bypass procedure, new openings are created in the airway wall connecting the damaged lung tissue to the natural airway. These pathways are supported and kept open by Exhale® drug-eluting stents manufactured by Broncus Technologies, Inc. Patients could see an immediate improvement in shortness of breath. Although this procedure is still under clinical investigation, feasibility data suggest it may hold promise for patients with emphysema. Results from the open-label Exhale feasibility study were published in the October issue of the Journal of Thoracic and Cardiovascular Surgery. Positive results included a statistically significant reduction in the amount of air trapped in the lungs and an improvement in breathing for patients at six months after the airway bypass procedure. The EASE trial is designed to see if these results hold in a randomized, controlled trial. Source: EurekAlert! 4/1/08

Appendix Removed Through Vagina in a U.S. First

On March 26, 2008, surgeons at University of California San Diego Medical Center removed an inflamed appendix through a patient’s vagina, a first in the United States. Following the 50-minute procedure, the patient reported only minor discomfort. Removal of diseased organs through the body’s natural openings offers patients a rapid recovery, minimal pain, and no scarring. Key to these surgical clinical trials is collaboration with medical device companies to develop new minimally invasive tools. The procedure, called Natural Orifice Translumenal Endoscopic Surgery (NOTES), involves passing surgical instruments through a natural orifice, such as the mouth or vagina, to remove a diseased organ such as an appendix or gallbladder. Only one incision is made through the belly button for the purpose of inserting a two millimeter camera into the abdominal cavity so the surgeons can safely access the surgical site. Santiago Horgan, MD, director of the medical center's Center for the Future of Surgery, is a world leader in minimally invasive surgeries, having performed 14 of these scarless NOTES procedures in the U.S. and Argentina. Horgan cites the critical role of biotechnology companies in bringing NOTES devices into the operating room for clinical trials. “The path to innovation is dynamic, requiring quick response from the companies developing the tools,” said Horgan, president of the Minimally Invasive Robotics Association. “Partnership with industry keeps us rolling from one success to another. The evolution of surgery to incisionless techniques is on the horizon.” Source: Newswise 3/28/08

Research Could Lead to Brain Tumor Therapies

Unique human in vitro model (cell culture) research currently under way at the Peninsula Medical School in southwest England is set to identify and develop therapies for the treatment of multiple tumors in the brain. The tumors are caused by mutations affecting a protein called merlin, which in turn cause cancers in a range of cell types, including Schwann cells in the brain. Schwann cells produce the sheaths that surround and insulate neurons. Although the tumors are benign, they are frequent, can be inherited, and the sheer number of them can overwhelm a patient, often leading to deafness and eventually death. Patients can suffer from 20 to 30 tumors at any one time, and the condition typically affects older children and adults. No therapy, other than invasive surgery aiming at a single tumor and which may not eradicate the full extent of the tumors, exists. Research at the Peninsula Medical School is led by Professor Oliver Hanemann. Working with human cells in vitro, Professor Hanemann and his team have secured initial success at reprofiling an existing drug, sorafenib; because they are using the cell culture model and reprofiling new cancer drugs, they do not need to carry out huge toxicity studies. This means they now can go straight to clinical trials and introduce therapies to patients sooner, rather than later, using sorafenib or similar drugs. Said Professor Hanemann: “Ours is a unique model and a unique approach to the issue. We are on the verge of working with inpatient clinics to trial our latest breakthrough, and we are investigating other therapeutic targets using other drugs.” He added: “Using human in vitro cell culture, which is the unique aspect of our work, allows us to move seamlessly and relatively quickly from lab-based biochemistry to drug therapies, clinical trials, and hopefully successful outcomes.” Source: EurekAlert! 3/24/08

Appendix Removed through Mouth, First in U.S.

On March 12, surgeons at the University of California San Diego Medical Center performed what is believed to be the country’s first removal of a diseased appendix through the mouth. This clinical trial procedure received approval for a limited number of patients by the university’s institutional review board, which oversees clinical research. “The purpose of this clinical trial is to test more ‘patient-focused’ techniques for minimally invasive surgery,” said Mark A. Talamini, MD, professor and chair of the Department of Surgery at the medical center. Santiago Horgan, MD, professor and director of the university's Center for the Future of Surgery, and Talamini, president elect of the Society of American Gastrointestinal and Endoscopic Surgeons, performed the surgery on Jeff Scholz, a 42-year-old California resident. India is the only other country to report such an operation. Horgan and Talamini used the FDA-cleared EndoSurgical Operating System (EOS) developed by USGI Medical, Inc. to perform the procedure. EOS was passed through the patient’s mouth and into the stomach, where a small incision was made in the stomach wall to pass the instrument through to the appendix for removal. Source: Newswise 3/17/08

Drug Tested for Preventing Muscle Fiber Death in Muscular Dystrophy

An investigational antiviral drug currently undergoing human trials in Europe for treating hepatitis C infections may have potential to reduce muscle cell damage in Duchenne and other forms of muscular dystrophy (MD). A research team led by Cincinnati Children’s Hospital Medical Center reported its results using three different mouse models of MD in a letter posted online March 16 by the journal Nature Medicine. The investigational drug, Debio-025, is a known inhibitor of the protein cyclophilin D, which regulates the swelling of mitochondria in response to cellular injury. Researchers decided to test the drug in mice engineered to carry MD after earlier laboratory tests showed that deleting a gene that encodes cycolphilin D reduced swelling and reversed or prevented the disease’s muscle-damaging characteristics. The drug is manufactured by DebioPharm S.A. of Lausanne, Switzerland, which provided Debio-025 for use in the study. Source: EurekAlert! 3/16/08

Massachusetts General Hospital Initiates Phase I Diabetes Trial

Scientists at the Massachusetts General Hospital have initiated a Phase I clinical trial to reverse Type 1 diabetes. The trial is exploring whether the promising results from the laboratory of Denise Faustman, MD, PhD, can be applied in human diabetes. Faustman’s previous studies have shown that mice with a form of diabetes that closely resembles Type 1 diabetes in humans can be cured. In the animal studies, a commonly used vaccine that provides protection against tuberculosis, called Bacillus Calmette-Guerin (BCG), was used effectively to deplete the abnormal immune cells that attack and destroy the insulin-producing cells of the pancreas. The first step in the human study, which is currently enrolling volunteers, is to determine whether the same strategy using BCG vaccination can be used to modify the abnormal autoimmune cells that are present in Type 1 diabetes, sometimes called “juvenile-onset” diabetes. “We are pleased to be starting human clinical trials,” said Faustman. “Human trials take time, but we are making the step from curing diabetes in mice to determining whether it will work in men and women with diabetes.” The Phase I trial is being supported largely through direct and fundraising support from the Iacocca Foundation, and through support from other donors and the Massachusetts General Hospital. Source: EurekAlert! 3/13/08

Radioimmunotherapy After Chemotherapy Safe and Effective for Follicular Non-Hodgkin's Lymphoma

Radioimmunotherapy with the radioactive drug yttrium-90 (90Y) ibritumomab tiuxetan, following chemotherapy with fludarabine and mitoxantrone, is feasible, well tolerated, and effective in patients with follicular non-Hodgkin's lymphoma (NHL). These are the conclusions of authors of an article published early online and in the April edition of The Lancet Oncology. Follicular lymphoma accounts for nearly 30 percent of all newly diagnosed NHLs, and is the most common form of lymphoma in the United States and Europe. The findings of various trials have shown that the combination of a chemotherapy regimen with rituximab (a nonradioactive targeted treatment for B-cell lymphomas) significantly increased progression-free survival compared to the same chemotherapy regimen alone. Researchers wanted to see if these benefits could be improved when, instead of rituximab, 90Y-ibritumomab tiuxetan was used. Researchers at the University of Bologna, Italy, studied 61 patients across 13 Italian institutions. All received six cycles of oral fludarabine and intravenous mitoxantrone; and 57 of these (43 with complete response [CR] and 14 with partial response [PR]) were deemed eligible for subsequent 90Y-ibritumomab tiuxetan. Twelve of the 14 PR patients achieved CR after the treatment; thus overall, 55 of 57 patients achieved CR after the combined treatment regimen. Furthermore, with a median follow-up of 30 months, three-year progression-free survival was estimated at 76 percent, and three-year overall survival at 100 percent. Source: EurekAlert! 3/12/08

Dermatology Team Finds Treatment for Rare “Life-Ruining” Condition

Dalhousie Medical School dermatologist Dr. Barrie Ross and his colleagues have successfully ended a 20-year quest to find a treatment for Familial Cold Autoinflammatory Syndrome (FCAS). The rare condition, triggered by exposure to cold, causes severe discomfort and physical incapacity. Through a clinical trial conducted at Capital Health in Halifax, Nova Scotia, Canada, Dr. Ross and his colleagues proved the overwhelming effectiveness of anakinra (Amgen Corp.'s Kineret), a receptor-blocking medication, to ease the pain and suffering caused by FCAS. The study results were published in the Journal of Cutaneous Medicine and Surgery. Dr. Ross had the rare honor of seeing his quest through from beginning to successful end. In 1986, the year her mother was diagnosed with kidney failure linked to FCAS, Anne Mallais visited Dr. Ross. She was on a crusade to find a cure for the debilitating condition that afflicts her and many members of her family. “From the time Anne came to see me, it was serendipity, the advancement of technology, and perseverance that led to the clinical trial and the discovery of a treatment,” says Dr. Ross. FCAS causes hives, fever, chills, myalgias, headache, stiffness, and swelling, among other symptoms. “It’s like you’re freezing from the inside out,” says Rachel Doherty. “Your whole body contracts until you warm up, which can take hours or days.” Doherty took over the crusade from her sister to find a cure; she participated in the clinical trial, as did seven other family members with long-standing FCAS. They received daily anakinra injections, and all experienced complete symptom relief within 24 hours of their first injection. The relief lasted through the treatment period, despite participants being subjected to cold on a daily basis. “The results were phenomenal,” says Dr. Ross. For Doherty it was surreal. “It was like one minute I was paralyzed and the next I was normal," she said. "When I went home, I walked around in circles not knowing what to do first.” About 600 people around the world are afflicted by FCAS. Source: Newswise 3/11/08

HPV Vaccine Reduces Abnormal Pap Test Results

A significant drop in abnormal Pap test results happened after girls and women were given a vaccine to prevent cervical cancer, according to a researcher at the University of Alabama at Birmingham. The findings show the vaccine, Merck & Co. Inc.’s Gardasil, appears to prevent the development of cell changes that lead to cervical disease. In testing, Gardasil reduced abnormal Pap test results by 43 percent compared to women not given the vaccine. The reduction was for tests that found precancerous changes called high-grade squamous intraepithelial lesions more than three years after women were given the vaccine. The vaccine reduced other abnormal Pap results, including milder premalignant cell changes, by 16 to 35 percent compared to women not given the vaccine. While the findings are not definitive regarding cancer prevention, they do signal the vaccine will spare thousands of women a diagnosis of cell abnormality or malignant changes that may lead to more tests and possibly surgery. The findings, presented March 10 at a meeting of the Society of Gynecological Oncologists, are a compilation of three separate trials involving more than 18,000 women, ages 16 to 26, in the United States, Europe, and Asia. All test subjects had normal Pap smear readings at the start of the trial. In addition to the drop in unwanted Pap results, the study found invasive procedures like cervical biopsies were performed up to 42 percent less in Gardasil recipients compared to women not given the vaccine. Source: Newswise 3/10/08

Cancer Risk Slightly Higher for Women in Discontinued Hormone Treatment Trial

A follow-up study of participants in the Women’s Health Initiative (WHI) clinical trial led by a University of North Carolina at Chapel Hill researcher has found that women who were taking the combined hormone therapy of estrogen plus progestin may have an increased risk of cancer since the intervention was stopped, compared to participants in the trial’s placebo group. However, the increased risks of heart disease, stroke, and blood clots—which had been seen in women taking the therapy as part of the WHI trial—have diminished in the three years since researchers stopped it, according to a study published in the March 5 issue of the Journal of the American Medical Association. The WHI trial of estrogen plus progestin—which included 16,608 healthy postmenopausal women—was originally designed to study what effect the hormone treatment would have on cardiovascular disease, cancer risks, and bone fractures. The trial was stopped in July 2002 after participants had been on the therapy for an average of 5.6 years because researchers saw an increased risk of breast cancer and cardiovascular disease in women randomly assigned to hormone therapy, compared with those who received a placebo. Since then, WHI researchers have examined the risks and benefits experienced by 15,730 trial participants who had follow-up visits from July 2002 to March 2005, after they stopped hormone therapy. Source: EurekAlert! 3/4/08

Malaria Vaccine Search Accelerated through Expansion of Human Challenge Tests

In a move that should expedite the clinical assessment of malaria vaccine candidates, the PATH Malaria Vaccine Initiative (MVI) and Seattle Biomedical Research Institute (SBRI) in March announced a new collaboration to establish a center devoted to testing the safety and efficacy of malaria vaccine candidates in humans. The new Human Challenge Center at SBRI will be one of only a handful of facilities of its kind worldwide and will help meet the growing demand to test new interventions against the deadly malaria parasite. The center will be the critical foundation of the Malaria Clinical Trials Center, which integrates basic science and clinical research uniquely focused on addressing the burden of malaria with the goal of bringing new solutions to the world. After a malaria vaccine candidate has been tested for safety in a small number of healthy adult volunteers, some candidates may undergo a challenge phase of testing. Volunteers vaccinated with a malaria vaccine candidate are deliberately infected with malaria through the bite of malaria-infected mosquitoes to assess whether or not the candidate vaccine can prevent or delay malaria infection. This human challenge phase of malaria vaccine development can provide researchers with valuable data to decide whether or not to move a vaccine candidate forward. The center will provide the high level of care required to ensure the safety of volunteers, in accordance with protocols approved by the U.S. Food and Drug Administration. Source: EurekAlert! 3/4/08

Costly Placebo Works Better than Cheap One

A 10-cent pill doesn't kill pain as well as a $2.50 pill, even when they are identical placebos, according to a provocative study by a behavioral economist at Duke University that was described in a letter in the March 5 edition of the Journal of the American Medical Association. The Duke researcher and a team of collaborators at the Massachusetts Institute of Technology used a standard protocol for administering light electric shock to participants’ wrists to measure their subjective rating of pain. The 82 study subjects were tested before getting the placebo and after. Half the participants were given a brochure describing the pill as a newly approved painkiller costing $2.50 per dose, and half were given a brochure describing it as marked down to 10 cents, without saying why. In the full-price group, 85 percent of subjects experienced a reduction in pain after taking the placebo. In the low-price group, 61 percent said the pain was less. The results fit with existing data about how people perceive quality and how they anticipate therapeutic effects, so the lead researcher wonders if prescription medications should offer cues from packaging, rather than coming in indistinguishable brown bottles. The findings also raise the question of how to give people cheaper medication, or a generic, without them thinking it won't work; and the possibility that doctors could use their enthusiasm for a medication as part of the therapy in the form of quality cues that might lead to a treatment having greater effectiveness in patients. Source: EurekAlert! 3/4/08

Newly Developed Antimalarial Medicine Treats Toxoplasmosis

A new drug that will soon enter clinical trials for treatment of malaria also appears to be 10 times more effective than the key medicine in the current gold standard treatment for toxoplasmosis, a disease caused by a related parasite that infects nearly one-third of all humans. In the March issue of PLoS Neglected Tropical Diseases, a research team based at the University of Chicago Medical Center shows that the drug, known as JPC-2056, is extremely effective against Toxoplasma gondii, the parasite that causes toxoplasmosis, without toxicity. The drug inhibits the action of an enzyme, dihydrofolate reductase (DHFR), produced by the family of parasites that includes those that cause toxoplasmosis and malaria. It is structurally distinct from the human DHFR. The new drug was effective against all malaria parasites, even those with multiple mutations that make them resistant to other antifolate medicines. Toxoplasma infection is probably the most common parasitic infection in the world, causing very significant disease in those who have immature immune systems or who are immune-compromised. The standard medicines to treat the infection can cause severe side effects, and many patients become hypersensitive to them. There are no medicines that can eliminate certain latent stages of the parasite's life cycle. There is no vaccine. The National Institutes of Health, the Research to Prevent Blindness Foundation, and donations from several private family foundations supported this research. Source: EurekAlert! 3/4/08

Research Collaboration to Focus on Anticancer Efforts

Advanced Viral Research Corp. (ADVR), which focuses on small-molecule anticancer drug discovery and development, in February announced a research agreement with Northeastern University. The company’s scientists will work with the university’s Department of Chemistry and Chemical Biology to identify how compounds such as AVR118, a Phase II clinical candidate, interact with clinically relevant molecular targets associated with cancer. In addition to providing greater clarity into how AVR118 exerts its cytoprotective effects, this work is expected to provide valuable insights for producing new generations of product with greater potency and ease of administration. Another important goal of this agreement is to apply ADVR's AFP Technology to identify new compounds with anticancer activity. AVR118 represents a new class of cytoprotective agent that targets, among other things, some of the most problematic symptoms associated with clinical cachexia, or the so-called wasting syndrome. In addition, AVR118 has been shown to possess topical wound-healing properties in animal models. Source: ADVR press release 2/25/08

Protein Shines Light on Cancer Response

A technique that specifically “tags” tumors responding to chemotherapy may offer a new strategy for determining a cancer treatment’s effectiveness within days of starting treatment, according to a new study by Vanderbilt-Ingram Cancer Center investigators. Appearing online ahead of print in Nature Medicine, the researchers report the identification of a small protein that specifically recognizes tumors responding to chemotherapy. They show that the protein, when tagged with a light-emitting molecule, can be used to visualize cancer response in mice just two days after starting therapy. The next step will be to move the technology into humans. The imaging technique used in mice (near-infrared) is not sensitive enough to penetrate deeply into human tissues, so the researchers are adapting the technology to an imaging modality commonly used in humans, called PET (positron emission tomography). This imaging peptide will enter clinical trials within about 18 months with one goal being to speed cancer drug development in the early phases of trials. Source: EurekAlert! 2/24/08

Scientists Move Toward Stem Cell Therapy Trials to Mend Bones

The United Kingdom Stem Cell Foundation, the Medical Research Council, and Scottish Enterprise, in partnership with the Chief Scientist’s Office in Scotland, are funding a £1.4 million project at the University of Edinburgh to further stem cell therapy for such conditions as osteoarthritis and severe bone trauma, with a view to setting up a clinical trial within two years. The research involves using a “bioactive scaffold” to protect the stem cells and stimulate their growth into bone or cartilage once they are placed in the affected area. The scaffold consists of a fairly rigid mesh structure, coated or impregnated with a drug that affects the patient’s cells. For nearly a decade, scientists have known broadly the right chemical conditions required to encourage undifferentiated stem cells taken from a patient's bone marrow to change into bone and cartilage cells in the laboratory. However, the use of the “bioactive scaffold” being developed at the University of Edinburgh aims to enable these cells to grow within the human body. The initial clinical trial resulting from the laboratory work is likely to involve nearly 30 patients. Source: EurekAlert! 2/18/08

New Technology for Early Detection of Lung Cancer Selected for Clinical Study

The science and engineering research university known as the New Mexico Institute of Mining and Technology and the firm Biomoda, Inc. have partnered with the New Mexico Department of Veterans Services to conduct a $350,000 clinical study using proprietary testing technology for detection of early lung cancer in the state's veterans. Biomoda's technology is based on a patented application that identifies cancerous or aberrant cells from samples of lung sputum. Cancerous cells glow red under fluorescent light and can be detected under a microscope. The technology is noninvasive and designed for cancer screening of large populations at a reasonable cost. Biomoda's team of experts includes representatives from TriCore Laboratories, Averion International, and Quintiles Consulting. The Black Veterans Association of New Mexico will assist with outreach to veterans. Source: PRNewswire 2/14/08

University to Lead Center of Excellence in Vaccine Commercialization and Research

The University of Saskatchewan will lead a $25.5 million national Center of Excellence for Commercialization and Research aimed at fast-tracking vaccine development for diseases of major public health concern, such as pandemic influenza, whooping cough, chlamydia, “mad cow” disease, and severe diarrheal diseases. The nonprofit research corporation will be known as the Pan-Provincial Vaccine Enterprise (PREVENT), and will operate with support from the Canadian government, the university, the Canadian Center for Vaccinology (a partnership among Dalhousie University, IWK Health Center, and QEII Health Center), and the B.C. Center for Disease Control. The activities of PREVENT will help reduce the risk of infectious diseases by taking promising early-stage vaccine candidates through preclinical development and Phase I human trials, thus adding significant value to them and increasing the chances of developing marketable vaccines. PREVENT will develop vaccines for both human and animal hosts, with a focus on pathogens transmitted from animals to humans for which there are currently no available vaccines. One example is respiratory syncytial virus, a major cause of respiratory disease in infants. PREVENT will also work to improve existing vaccines by evaluating new formulations that reduce adverse effects, enhance protection, improve vaccine delivery, and lower production costs. Source: Newswise 2/14/08

Hospital Set to Begin Clinical Trial to Help Emphysema Sufferers

New York Methodist Hospital in February announced the start of the EASE (Exhale Airway Stents for Emphysema) trial, an international, multicenter study of an investigational treatment that may offer a minimally invasive option for those suffering with advanced emphysema. The study focuses on a procedure called airway bypass. During airway bypass, physicians will use a flexible bronchoscope to go through the mouth and into the airways to create new small pathways and place up to six Exhale® drug-eluting stents—manufactured by Broncus Technologies, Inc.—to allow the trapped air in the lung to escape. Patients could see an immediate improvement in dyspnea (shortness of breath). Source: EurekAlert! 2/4/08

Malaria Vaccine Trials Begin Using Chimpanzee Virus

Trials are under way, funded by the Wellcome Trust, for a new vaccine to combat the most deadly form of malaria. For the first time, researchers will use a virus found in chimpanzees to boost the efficacy of the vaccine. The trials will take place at the University of Oxford's Jenner Institute. The vaccine being developed by a university team in collaboration with Okairòs uses the company’s genetically modified chimpanzee adenovirus to produce the malaria antigen and to stimulate a response to the vaccine in the body. Using a chimpanzee adenovirus ensures that a recipient is unlikely to have resistance to this component of the vaccine. The university team is currently recruiting more volunteers for the first trials, which are to assess the safety of the vaccine and the response of the immune system. The team hopes to generate a response from CD8+ T-cells, which should kill the malaria-causing parasites when they enter the liver. Source: EurekAlert! 1/31/08

Researchers Seek HIV Vaccine Trial Participants

University of Pennsylvania School of Medicine researchers are recruiting healthy, HIV-negative adults to participate in a Phase I clinical trial of an experimental HIV vaccine called PENNVAX-B, a DNA-based vaccine that is made using synthetic DNA-based HIV genes. Approximately 120 trial participants will be divided into several vaccine groups to test the safety and immunogenicity of various cytokine “molecular adjuvants” that previous studies have shown to help boost immune response to the vaccine in monkeys. The study, which also includes a site at the University of Alabama at Birmingham, is expected to take two years. The vaccine development and the clinical trial are sponsored by the Division of AIDS at the National Institute of Allergy and Infectious Diseases, the National Institutes of Health, and the Department of Health and Human Services. The study is conducted under the HIV Vaccine Trials Network. Wyeth Pharmaceuticals is an industry partner for the vaccine. Source: Newswise 1/30/08

University Spinoff to Test Regenerative Wound-Healing Gel

First-String Research, Inc., a spinoff biotechnology company from the Medical University of South Carolina, has begun the human clinical trial process for a wound-healing peptide gel. Already past the preliminary approval stages, the first-in-human trial will take place in Switzerland. Initial preclinical studies have suggested the gel’s efficacy and safety in regenerating new tissue, instead of scar tissue, in order to heal wounds better and faster. In the clinical trial, four different doses of the gel will be administered to study participants with deep wounds. The bioengineered peptide is based on a naturally occurring protein in the body that helps regulate communication between cells. This peptide accelerated wound healing and tissue regeneration with significantly reduced scarring in laboratory animal tests, which leads researchers to believe that it will promote faster healing, reduced scarring, and restoration of more normal-looking skin during human clinical trials. Source: Newswise 1/29/08

Common Drug-Releasing Coronary Stents Appear to Have Similar Clinical Outcomes

A comparison of use of the first two commercially available drug-releasing coronary stents among patients in “everyday clinical practice” indicates no significant differences for outcomes, according to a study in the January 30 issue of JAMA. Approval of such stents was based on results of relatively small trials of selected patients; however, in routine practice, stents are used more broadly. Researchers at the University of Copenhagen compared the efficacy and safety of sirolimus-eluting and paclitaxel-eluting stents in a trial of 2,098 men and women randomized to receive one or the other type of stent at five university hospitals in Denmark. The researchers found that 98 patients (9.3 percent) experienced major adverse cardiac events in the sirolimus-eluting stent group and 114 (11.2 percent) in the paclitaxel-eluting stent group. The stent thrombosis rates were 27 (2.5 percent) in the sirolimus-eluting stent group and 30 (2.9 percent) in the paclitaxel-eluting stent group. Source: Newswise 1/29/08

New Vaccine Against Deadliest Strain of Avian Flu Tested

A vaccine against the most common and deadliest strain of avian flu, H5N1, has been engineered and tested by researchers at the University of Pittsburgh’s Center for Vaccine Research and Novavax Inc. According to a study published by the Public Library of Science in the January 30 issue of PLoS ONE, the vaccine produced a strong immune response in mice and protected them from death following infection with the H5N1 virus. The vaccine is being tested in humans in an early-phase clinical trial. Unlike other avian flu vaccines, which are partially developed from live viruses, the vaccine uses a virus-like particle that is recognized by the immune system as a real virus but lacks genetic information to reproduce, making it a potentially safer alternative for a human vaccine. Given the evolving nature of H5N1, the vaccine was engineered to encode genes for three influenza viral proteins to offer enhanced protection against possible new strains of the virus. Source: EurekAlert! 1/29/08

Participants in Studies used as Basis for Medicare Decisions Differ from Beneficiaries

The clinical trials used by Medicare for making decisions about coverage for cardiovascular products or services include participants who differ from Medicare beneficiaries in age, sex, and country of residence, according to a report by University of California at San Francisco School of Medicine researchers in the January 28 issue of Archives of Internal Medicine. The researchers performed a meta-analysis of all trials included in technology assessments considered by the Centers for Medicare and Medicaid Services advisory panel between 1998 and 2006. For the panel’s six meetings, 141 studies with a total of 40,009 participants were analyzed. Compared to Medicare beneficiaries, clinical trial participants were an average of 60.1 years versus 74.7, 75.4 percent versus 41.8 percent male, and 60 percent versus zero from countries outside the United States. “The trials are conducted mostly in younger, healthier, male, non–U.S. populations,” the authors write. “Medicare beneficiaries, on the other hand, are mostly older women with comorbid [co-occurring] conditions. The clinical trials primarily relied on to inform national coverage decisions simply do not reflect the Medicare patient population. Compounding this problem, data frequently are not reported by age, sex, and race.” Women and the elderly are the most likely to be affected by these disparities and should be included in more clinical trials, the authors note. Source: EurekAlert! 1/28/08

New Method Enables Design and Production of Novel Drugs

A new chemical synthesis method that provides a more efficient and economical method than traditional ones for designing and manufacturing novel pharmaceutical compounds is described by its University at Buffalo developers in a review article in a recent issue of Nature. The chemistry, the basis of a new biotech startup company called Dirhodium Technologies, LLC in Buffalo, N.Y., has the potential to improve dramatically the design and production of new drugs based on small-molecule organic compounds, which comprise the great majority of new drug applications. The chemical strategy depends on the use of a proprietary, rhodium-based catalyst, one gram of which is capable of producing 10 kilograms of a pharmaceutical product. Available through chemical supply companies, the reagents are being used by pharmaceutical scientists in both industry and academia. Already, one major pharmaceutical company is using the reagents to synthesize a compound now in clinical trials. So far, the new synthesis strategy has generated compounds that have potential activity against a broad range of disease states, from cancer to central nervous system disorders, such as depression, to inflammatory and microbial diseases and medications for treating cocaine addiction. Source: EurekAlert! 1/23/08

Researchers: Pros, Cons of Prostate Cancer Drug Should be Considered

Findings by University of Texas Southwestern Medical Center researchers encourage men to weigh both the potential benefits and side effects of the drug finasteride before taking it to prevent prostate cancer. In a recent online issue of Cancer, the researchers analyzed data gathered by the National Cancer Institute’s Prostate Cancer Prevention Trial. The trial, which began in 1993, was designed to test whether finasteride could prevent prostate cancer in men 55 years of age and older. It was stopped early in 2003 when an analysis showed that finasteride reduced the risk of developing prostate cancer by 25 percent. However, the new analysis of the data indicates that cost effectiveness and quality-of-life issues associated with taking the drug are not clear cut. The data show that in addition to preventing prostate cancer, finasteride reduced urinary-tract symptoms associated with benign prostatic hyperplasia. It also decreased sexual desire and caused impotence in 5 percent of the trial participants. Some participants who did develop prostate cancer also had high-grade tumors, although there is ongoing debate whether this result might have been due to sampling bias. Source: EurekAlert! 1/21/08

University-Funded Pilot Studies Could Lead to Clinical Trials

The Rockefeller University Center for Clinical and Translational Science has announced the recipients of its 2008 Pilot Project grants. Eight Rockefeller researchers will each receive $25,000 from the center to fund early studies in translational science that, if successful, might lead to clinical trials. The center and the grant program, now in their second year, were established through funds from a Clinical and Translational Science Award the university received from the National Center for Research Resources of the National Institutes of Health. In its first year, the program provided $165,000 for nine clinical studies. The new pilot projects include examinations of the efficacy of poly IC and Ampligen as adjuvants for an HIV vaccine targeted at DEC-205, an antigen receptor on dendritic cells; the mechanism of action of disulfiram, a drug commonly used to treat chronic alcoholism, with regard to cocaine addiction; and the generation of patient-specific human hepatocytes as a renewable source for primary liver tissue. Source: Newswise 1/7/08

Novel Anti-Cancer Strategy Moves from Laboratory to Clinic

Researchers at Emory University and Semafore Pharmaceuticals have developed a novel anti-tumor compound that represents a distinct strategy: targeting one of the most important "intercept points" for cancer cells. The strategy is to shut down the transmission of a large number of growth signals in cancer cells at once by targeting a class of enzymes called PI-3 kinases, which represent an intercept point and occupy valuable real estate in almost every cell in the body. The compound, called SF1126, is active against prostate, breast, and renal cancer, as well as multiple myeloma, neuroblastoma, glioblastoma, and rhabdomyosarcoma. At the end of 2007, doctors in Arizona and Indiana began to test SF1126 in a Phase I clinical trial in people with solid tumors. Another Phase I trial for multiple myeloma patients will begin at Emory's Winship Cancer Institute and elsewhere in 2008. It is anticipated that SF1126 will enter pediatric cancer trials within one year. Source: EurekAlert! 1/3/08

Effects of High-Dose Vitamin C on Non-Hodgkin's Lymphoma Patients to be Studied

Scientists at Thomas Jefferson University Hospital and Jefferson’s Kimmel Cancer Center have received approval for a first-of-its-kind study on the effect of high-dose vitamin C on non-Hodgkin's lymphoma patients. In conjunction with the National Institutes of Health (NIH), the researchers will study whether high doses of vitamin C can slow the progression of the deadly disease. Recent research conducted by the NIH collaborators of this study has shown that when given in sufficient amounts intravenously, vitamin C converts to hydrogen peroxide. When applied to certain non-Hodgkin's lymphoma cells in the laboratory, the converted hydrogen peroxide kills them while leaving the surrounding healthy cells intact. The study will begin with 20 non-Hodgkin's lymphoma patients who have failed standard therapy. Each study participant will be given varied intravenous doses of vitamin C three times a week. The patients will be evaluated and monitored for progression of their disease. Source: Newswise 1/2/08

Quantum Researchers Discover Fast-Acting Cyanide Antidote

University of Minnesota Center for Drug Design and Minneapolis VA Medical Center researchers have discovered a new fast-acting antidote to cyanide poisoning. The antidote has potential to save lives of those who are exposed to the chemical—namely firefighters, industrial workers, and victims of terrorist attacks. Current cyanide antidotes work slowly and are ineffective when administered after a certain point, said Steven Patterson, PhD, principal investigator and associate director of the drug design center. Patterson is developing an antidote that was discovered by retired University of Minnesota Professor Herbert Nagasawa. The research will be featured in the Journal of Medicinal Chemistry. The antidote was tested on animals and has been exceptionally effective, Patterson said. Researchers hope to begin human clinical trials during the next three years. Source: EurekAlert! 12/27/07

$10 Million Grant Targets Trachoma Research

The Johns Hopkins University has received a $10 million grant from the Bill & Melinda Gates Foundation to lead a consortium that will study ways to improve the treatment of trachoma, the leading infectious cause of blindness worldwide, primarily in poor and rural regions. The partners include research teams at the Johns Hopkins University’s School of Medicine and Bloomberg School of Public Health, the London School of Hygiene and Tropical Medicine, the University of California at San Francisco, Pfizer, the World Health Organization, and the Trachoma Control Programs at the Ministries of Health in Tanzania, Ethiopia, and The Gambia. The grant will fund trials of surgical devices and antibiotics in countries hosting three distinct infection scenarios: The Gambia, where the disease is on the verge of elimination; Tanzania, where treatment programs are in place and the disease is on the decline; and Ethiopia, where treatment programs have not yet started. Source: Newswise 12/20/08

Computational Chemical Method Aims to Speed Drug Development

New research led by a Virginia Tech chemist may someday help natural-products chemists decrease by years the amount of time it takes for the development of certain types of medicinal drugs. The research involves computations of optical rotation angles on chiral (non-superimposable) molecules. Many chiral molecules are important for medical treatment for illnesses ranging from acid-reflux to cancer. The term “chiral” means that two mirror images of a molecule cannot be superimposed onto each other. In other words, some are “left-handed” and some are “right-handed.” For chemists, it is often vital to determine which “hand” of a molecule they are using, as the two can cause different reactions; this is done through time-consuming synthesis of the molecule and the use of a process known as polarimetry. The new research applies the theory of quantum mechanics to devise computational methods in order to eliminate having to create a synthetic molecule, the handedness of which must still be determined. Source: EurekAlert! 12/20/07

Promising Results for Pilot Trial of Wearable Hemodialysis Device

A pilot trial of a wearable hemodialysis device to improve the quality of life for patients with kidney failure has delivered promising results. These are the conclusions of United Kingdom–based researchers with the University College London Centre for Nephrology and the University College Medical School who studied five men and three women with end-stage kidney failure who were established on regular hemodialysis and fitted with the wearable hemodialysis device for between four and eight hours. The researchers found there were no important cardiovascular changes and no adverse changes in serum electrolytes or the acid-base balance in the patients’ blood. The patients stated unanimously that they would recommend the device to other patients. In an article about the trial in The Lancet, the authors conclude by calling for larger trials of the device to confirm safety and efficacy of the treatment. Source: EurekAlert! 12/13/07

Vanderbilt to Evaluate Investigational Device for Type 2 Diabetics

Vanderbilt Medical Center in Tennessee is seeking local residents with Type 2 diabetes who are overweight to participate in a randomized, double-blind, controlled national clinical study evaluating an implantable investigational device, the TANTALUS System, which delivers electrical pulses to the stomach when a person eats. The device’s safety and efficacy will be studied, as well as its impact on weight loss, blood pressure, and other clinical and metabolic parameters. The system is based on new technology called Gastric Contractility Modulation, which is designed to sense naturally occurring electrical activity of the stomach in real time and automatically apply electrical stimulation treatment during meal times. Source: Newswise 12/10/07

Government Funding Backs Continued Testing of Vaccines

The National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH, has renewed a contract with the University of Maryland School of Medicine to conduct clinical trials of promising vaccines and therapies for infectious diseases. The school’s Center for Vaccine Development (CVD) will receive $23.7 million over seven years as a Vaccine and Treatment Evaluation Unit (VTEU) for NIAID. The CVD VTEU and seven other VTEUs nationally will enhance NIAID's ability to respond quickly to emerging public health needs. The program has facilitated the development of vaccines for pandemic and seasonal influenza, whooping cough, Norwalk virus, herpes, malaria, dysentery, cholera, and typhoid fever. New and improved vaccines to protect the public against a bioterrorism threat with smallpox, anthrax, and other diseases have also been tested. Most recently, the CVD VTEU participated in a large-scale trial to evaluate the seasonal influenza vaccine Fluarix for use in healthy adults in the United States. Source: University of Maryland 11/29/07

Gene Therapy Safety Trial for Childhood Blindness Under Way

Three decades have passed since gene therapy pioneer William W. Hauswirth, PhD, and his colleagues at the University of Florida began work on a virus that could safely deliver corrective genes into living animals. It has been six years since a multi-university team used gene therapy to give sight to puppies born with a defect that causes blindness. Now the gene-transfer technique is being tested for safety in people in a Phase I clinical research study conducted by the University of Pennsylvania and the University of Florida, with support from the National Eye Institute of the National Institutes of Health. In all, six adults and then three children between the ages of 8 and 17 will undergo the gene-transfer procedure over the next year or more before safety data are fully evaluated. Source: EurekAlert! 11/19/07

New HPV Vaccine Under Study

A new vaccine against nine of the most harmful strains of human papillomavirus (HPV) is under study at the Medical College of Georgia. The nine-valent vaccine is being compared to Gardasil, which was approved by the U.S. Food and Drug Administration in 2006. Gardasil protects against HPV types 16 and 18, which cause about 70 percent of HPV-related cervical cancer cases, and types 6 and 11, which cause about 90 percent of genital wart cases. The new drug could prevent infection from those four types and five other cancer-causing types. Like Gardasil, the new vaccine contains proteins that form virus-like particles that assemble into a hollow sphere resembling HPV’s protective coating. Although the sphere lacks the actual viral DNA on the inside, the body is tricked into making antibodies to protect against the real thing. Source: EurekAlert! 11/19/07