December 21, 2007

Grant helps spur pursuit of new Parkinson’s drugs

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Jeffrey Conn, Ph.D.

Grant helps spur pursuit of new Parkinson’s drugs

A drug discovery team at Vanderbilt University Medical Center led by Jeffrey Conn, Ph.D., has been awarded a $4.4 million “LEAPS” grant by the Michael J. Fox Foundation for Parkinson's Research to jump-start development of a new class of Parkinson's disease drugs.

“Dopamine replacement therapies have long been considered the 'gold standard' of Parkinson's treatment. But they lose efficacy over time, alleviate only some of Parkinson's disease symptoms, and cause side effects that can be as debilitating as the disease itself,” said Katie Hood, CEO of the Michael J. Fox Foundation.

“Patients don't think this status quo is good enough and neither does our foundation,” Fox said in a prepared statement. “Dr. Conn and his colleagues are aiming to bring about a 180-degree turn in Parkinson's disease treatment by developing an entirely new class of drugs that would bypass the dopamine system altogether.”

The funding was awarded under the foundation's 2007 LEAPS (Linked Efforts to Accelerate Parkinson's Solutions) initiative, which is designed to bring together “all-star” teams of researchers to address questions with significant practical impact on the treatment of Parkinson's disease.

In previous work, Conn's group showed that increasing the activity of a specific glutamate receptor, mGluR4, alleviated symptoms of Parkinson's in an animal model.

In further work supported by the foundation's Target Validation initiative, his team identified molecules that increase mGluR4 activity.

During the next three years, the researchers will use a combination of medicinal chemistry, molecular biology, and animal studies to engineer these molecules into a compound that can be clinically tested for use as a drug that could provide sustained symptomatic relief.

“At that point,” Conn said, “we may partner with a large pharmaceutical company.”

Early animal studies suggest that some of the molecules may slow progression of Parkinson's disease. While there are no guarantees that humans will respond in the same way, if they do, “it would be the first-ever treatment to be successful in slowing progression,” he said.

Conn, a professor of Pharmacology, directs the Vanderbilt Program in Drug Discovery. His LEAPS team includes:

David Weaver, Ph.D., director of the Vanderbilt Institute of Chemical Biology (VICB) high-throughput screening facility and head of new leads discovery in the Program in Drug Discovery, who will oversee the high-throughput screening to identify initially promising lead compounds;

Colleen Niswender, Ph.D., head of the molecular pharmacology team in the Program in Drug Discovery, who will screen lead compounds in cell-based assays to determine which hold the most promise to move on to testing in animal models;

Carrie Jones, Ph.D., head of the in-vivo and behavioral pharmacology group in the Program in Drug Discovery, who will spearhead the screening of lead compounds in rodent behavior models of Parkinson's disease;

Yoland Smith, Ph.D., professor of Neurology at the Yerkes National Primate Research Center at Emory University, who will oversee testing of the most promising lead compounds in the final preclinical phase of the project; and

Craig W. Lindsley, Ph.D., who directs the medicinal chemistry core in the Program in Drug Discovery, the Chemistry Center in Vanderbilt's Molecular Libraries Screening Center Network and the VICB synthesis core.

Lindsley will hold ultimate responsibility for optimizing the compound that will be tested in the clinic.