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The Michael J. Fox Foundation Awards $2 Million to Shed Light on Role of LRRK2 and Alpha-Synuclein Genes in Parkinson's Disease

NEW YORK, Jan. 15 /PRNewswire-USNewswire/ --- The Michael J. Fox Foundation for Parkinson's Research today announced approximately $2 million in total funding for seven research studies aiming to advance the ability of the Parkinson's research field, and drug makers, to therapeutically target two genes -- LRRK2 and alpha-synuclein -- that play a major, but still only partially understood, role in Parkinson's disease.

"Critical Challenges is uniquely designed to increase researcher focus on specific research challenges standing in the way of therapeutic progress," said Katie Hood, chief executive officer. "In this round, our research staff canvassed the world's leading PD experts to identify the precise issues holding up LRRK2 and alpha-synuclein drug development. We then structured our funding to incentivize scientists to look for the exact answers that will break down those roadblocks and allow work to move forward with greater impact. As in everything we do, our ultimate goal is to advance scientific solutions that can tangibly improve patients' quality of life."

LRRK2 and alpha-synuclein were selected for study under the first funding round of MJFF's Critical Challenges in PD program following a survey of the field by the Foundation's research staff and advisors. Alpha-synuclein was the first gene associated with PD, and pathological clumping of the protein product of the alpha-synuclein gene within cells of the brain represents a nearly universal thread linking multiple forms of Parkinson's. The association of the LRRK2 gene to PD was discovered more recently but appears to contribute to a substantial number of Parkinson's cases -- as high as 40 percent in some ethnic groups.

Investigators awarded under the alpha-synuclein challenge will look at various ways in which disease-related modifications of alpha-synuclein might lead to toxic effects. Hilal Lashuel, PhD, of Swiss Federal Institute of Technology Lausanne in Switzerland and Chris Rochet, PhD, of Purdue University will determine which modified forms of alpha-synuclein have the greatest effects on aggregation and toxicity to dopamine neurons. A third investigator, Deniz Kirik, MD, PhD, of Lund University in Sweden, will test the hypothesis that the toxicity of alpha-synuclein may be enhanced by interaction with dopamine itself, which might help further explain the selective vulnerability of these cells in PD.

The four investigators awarded under the LRRK2 challenge all seek to test whether an abnormal increase in LRRK2's enzymatic function triggers toxicity. Chenjian Li, PhD, of Weill Medical College of Cornell University and Zhenyu Yue, PhD, of Mount Sinai School of Medicine are each developing mice genetically engineered to express mutant forms of the LRRK2 gene, including a form that lacks enzymatic function, to directly test the hypothesis. Two other investigators, Romain Zufferey, MD, PhD, of Swiss Federal Institute of Technology and Andrew West, PhD, of the University of Alabama at Birmingham, will perform similar studies but will instead deliver the modified LRRK2 gene directly to brain cells using modified viruses, technology similar to that used in gene therapy.

Grant abstracts and researcher bios for all projects are available on the Foundation's Web site,

About The Michael J. Fox Foundation

Founded in 2000, The Michael J. Fox Foundation for Parkinson's Research is dedicated to ensuring the development of a cure for Parkinson's disease within this decade through an aggressively funded research agenda. The Foundation has funded over $112 million in research to date.

SOURCE Michael J. Fox Foundation
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