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Parkinsonís disease research highlighted

BY: BILL SNYDER

10/23/2009 - 

Conn

Conn

Researchers at Vanderbilt University Medical Center have reached a milestone in the development of potential new drugs for Parkinson's disease that may avoid the limitations of current therapy.

They have identified two drug-like molecules that, when given systematically in an animal model, reduce the symptoms of Parkinson's disease by acting on a specific glutamate receptor in the brain.

Jeffrey Conn Ph.D., director of the Vanderbilt Drug Discovery Program and leader of the research team, described the discovery at the recent Parkinson's Disease Therapeutics Conference, hosted by the New York Academy of Sciences and The Michael J. Fox Foundation for Parkinson's Research.

“If we can develop a molecule that has the right properties and does not have toxicity, we really believe this has an opportunity to have a major impact for Parkinson's patients,” said Conn. “Nothing could be more exciting than that … Nothing could be more satisfying.

“Obviously there are no guarantees,” Conn cautioned. But if progress continues, clinical trials in patients with Parkinson's disease could begin sometime in 2013, he said.

The Michael J. Fox Foundation for Parkinson's Research, which is funding the Vanderbilt study, has posted more information on Conn's work on its Web site at www.michaeljfox.org/research.

An estimated 1.5 million Americans have Parkinson's disease, a progressive brain disorder characterized by uncontrollable muscle tremors, rigidity and other symptoms. It is caused by the death of nerve cells in a specific brain region that produce the neurotransmitter dopamine.

Dopamine replacement therapy can relieve symptoms, but it also causes side effects and eventually becomes less effective as the disease progresses.

In previous studies, Conn and others have found that they could relieve symptoms of Parkinson's disease in animal models by activating a specific brain receptor called metabotropic glutamate receptor or mGluR4.

In their latest finding, the Vanderbilt researchers have found two compounds that act on mGluR4 and, when given systemically in an animal model of Parkinson's disease, get to the brain and relieve motor symptoms, including rigidity and akinesia or a “freezing” of certain motor muscles. Further animal testing will be required before tests in humans can begin.

But, said Conn, the identification of these molecules is “a big step forward.”

The Vanderbilt work has been supported since 2007 by a $4.4 million “LEAPS” (Linked Efforts to Accelerate Parkinson's Solutions) grant from the Fox Foundation.

Conn's colleagues in this effort include Colleen Niswender, Ph.D., Corey Hopkins, Ph.D., Carrie Jones, Ph.D., Craig Lindsley, Ph.D., and David Weaver, Ph.D.

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