NEWYORK, NY — The Michael J. Fox Foundation has awarded $4.4 million to jump-start the development of a new class of symptomatic Parkinson’s disease drugs targeting glutamate receptor mGluR4. The funding was awarded to a multidisciplinary team of researchers led by Jeffrey Conn, PhD, of VanderbiltUniversity under the Foundation’s LEAPS (Linked Efforts to Accelerate Parkinson’s Solutions) 2007 initiative.
The LEAPS 2007 program was funded with a lead gift from the Edmond J. Safra Philanthropic Foundation. The Edmond J. Safra Philanthropic Foundation has been one of the most steadfast supporters of The Michael J. Fox Foundation since its inception.
“Dopamine replacement therapies have long been considered the ‘gold standard’ of Parkinson’s treatment. But they lose efficacy over time, alleviate only some of PD’s symptoms, and cause side effects that can be as debilitating as the disease itself,” said Katie Hood, CEO of MJFF. “Patients don’t think this status quo is good enough, and neither does our Foundation. Dr.Conn and colleagues are aiming to bring about a 180-degree turn in PD treatment by developing an entirely new class of drugs that would bypass the dopamine system altogether.”
The death of dopamine neurons is a hallmark of PD pathology, and Parkinson’s scientists traditionally have focused their efforts on modulating aspects of the dopamine system. But recent insights into the physiology of the basal ganglia (a brain region affected in Parkinson’s disease) have shed light on the potential for treatments that could alleviate PD symptoms by “resetting” brain circuits. The glutamate system in particular has shown promise as a target for such treatments.
Glutamate, like dopamine, is a neurotransmitter — a signaling molecule that plays a role in transporting brain messages and controlling body functions. In previous work, Dr.Conn showed in an animal model that increasing activity of a specific glutamate receptor, mGluR4, may alleviate symptoms of Parkinson’s. In further work supported by MJFF’s Target Validation initiative, his team identified molecules that increase mGluR4 activity. The researchers will now 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.
LEAPS are multi-year, multi-million, multi-disciplinary projects that bring together “all-star” teams of researchers to address questions with significant practical impact on the treatment of Parkinson’s disease. Continued funding is dependent on completion of predetermined milestones at specific stages.
In addition to coordinating principal investigator Dr.Conn, who is professor of pharmacology and director of the Vanderbilt Program in Drug Discovery, this LEAPS team includes:
C. David Weaver, PhD, Research Associate Professor of Pharmacology; Director, Vanderbilt Institute of Chemical Biology High-throughput Screening Facility; Director, New Leads Discovery, Vanderbilt Program in Drug Discovery — Dr. Weaver will oversee the high-throughput screening to identify initially promising lead compounds.
Colleen Niswender, PhD, Research Assistant Professor, Department of Pharmacology; Head, Molecular Pharmacology Team, Vanderbilt Program in Drug Discovery — Once lead compounds have been identified through high-throughput screening, Dr. Niswender will be responsible for screening them in cell-based assays to determine which hold the most promise to move on to testing in animal models.
Carrie K. Jones, PhD, Research Associate Professor, Department of Pharmacology; Head, In Vivo and Behavioral Pharmacology Group, Vanderbilt Program in Drug Discovery — Dr. Jones will spearhead the screening of lead compounds in rodent behavior models of Parkinson’s disease.
Yoland Smith, PhD, Professor, Department of Neurology, Yerkes National Primate Research Center, Emory University — Dr. Smith, an expert in the neurophysiology of primate models of Parkinson’s, will oversee the testing of the most promising lead compounds in the final preclinical phase of the project.
Craig W. Lindsley, PhD, Associate Professor of Pharmacology and Chemistry; Director of Medicinal Chemistry, Vanderbilt Program in Drug Discovery; Director, Vanderbilt University MLSCN (Molecular Libraries Screening Center Network) Chemistry Center and Vanderbilt Institute of Chemical Biology Synthesis Core — Dr. Lindsey, a medicinal chemist, will hold ultimate responsibility for optimizing engineering of the compound that will be tested in the clinic.
To read a grant abstract and researcher bios, please visit www.michaeljfox.org.