VMAT2, a Drug Target Implicated in Multiple CNS Disorders, is Focus of Scientific Symposium

WASHINGTON, March 4, 2005 – PRNewswire – Experts in neurology, movement disorders, molecular genetics and vesicular biology convened this week in Washington, D.C. to discuss exciting current and emerging biology and genetics of the vesicular monoamine transporter 2 (VMAT2) and its roles as a target for brain imaging and pharmaco-therapeutics. The symposium took place on Thursday, March 3 during the 7th Annual Meeting of the American Society for Experimental NeuroTherapeutics (ASENT) and especially focused on roles of VMAT2 modulators in treatment of hyperkinetic movement disorders.

"VMAT2 is critical to the function of important brain chemical transmitters that are intimately involved in controlling our bodies' voluntary and involuntary movements," said George Uhl, M.D., Ph.D., Chief, Molecular Neurobiology Branch, National Institute of Drug Abuse, National Institutes of Health, Department of Health and Human Services and moderator of the VMAT2 discussion panel. "Individual differences in VMAT2 and our improving abilities to alter its function through targeted drug therapies are both exciting new developments that have broad implications for treating CNS disorders."

Results of late-stage clinical studies evaluating tetrabenazine, an investigational dopamine depleter that works by blocking VMAT2, were presented during the symposium by Frederick J. Marshall, M.D., Assistant Professor of Neurology and Principle Investigator, Clinical Trials Coordination Center, University of Rochester, New York. A randomized, double-blind, placebo-controlled study involving 84 patients with Huntington's Disease (HD) examined the efficacy of tetrabenazine versus placebo in treating chorea associated with HD. Patients were randomized to receive tetrabenazine (n=54) or placebo (n=30) for 12 weeks. The primary outcome was the change from baseline in chorea score as measured by the Unified Huntington's Disease Rating Scale (UHDRS). Secondary outcomes included the Clinical Global Impression (CGI) score, a clinician-rated scale used to assess the severity of illness and change in clinical condition over time.

After 12 weeks, the adjusted mean tetrabenazine chorea score declined by 5.0 points, while scores for the placebo group declined by 1.5 points (p<0.0001). Tetrabenazine was superior to placebo as assessed by the CGI scale (p = 0.007). Forty-eight patients (89%) in the tetrabenazine group had at least one adverse effect, compared with 21 subjects (70%) in the placebo group (p = 0.03).

"Tetrabenazine selectively binds to VMAT2," said Dr. Marshall. "This property may provide significant advantages over existing therapies because it is associated with greater efficacy and fewer, more manageable side effects."

In addition to Drs. Uhl and Marshall, leaders of the symposium titled VMAT2: Molecule, Gene, Man and Drug Responses, included Lee Eiden, Ph.D., Chief, Section of Molecular Neuroscience at the National Institute of Mental Health, and Kirk Frey, M.D., Ph.D., Professor of Neurology and Radiology and Senior Research Scientist, Mental Health Research Institute, The University of Michigan.

In his introductory remarks, Dr. Eiden noted, "VMAT2 acts as a valve for loading neurotransmitters into vesicles for release across brain synapses, where nerve impulses pass from one neuron to another. VMAT2 regulates the amount of neurotransmitter released with each impulse, making it a logical drug target for CNS disorders in which excessive transmitter release is at fault."

Dr. Frey presented interesting data on use of VMAT2 radioligands to characterize pathology in patients with neurodegenerative disorders, including Parkinson's disease and diffuse Lewy body disease. According to Dr. Frey, VMAT2 imaging studies in subjects with Tourette Syndrome suggest increased binding, particularly in the ventral striatum.

The American Society for Experimental NeuroTherapeutics (ASENT) brings together government, academia, the pharmaceutical industry, and advocacy groups in the field of neurological diseases to promote dialogue and cooperation among these groups. ASENT provides a forum for discussions among those interested in neurotherapeutics, it develops and disseminates information and seeks consensus on matters germane to the organization's mission. The Society accomplishes its mission through scientific forums, such as its Annual Meeting, and its quarterly journal, NeuroRX. For more information, visit www.asent.org.

SOURCE American Society for Experimental NeuroTherapeutics
Web Site: www.asent.org