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Scripps Research scientist awarded $500,000 grant to study Parkinson's disease
Date:10/26/2011

JUPITER, FL, October 26, 2010 The Scripps Research Institute has been awarded a $500,000 grant by the Michael J. Fox Foundation to study a pair of genetic mutations that could lead to a new and potentially vital therapeutic target for Parkinson's disease, a progressive and fatal neurodegenerative disorder.

Philip LoGrasso, PhD, a professor in molecular therapeutics and senior director for drug discovery at Scripps Florida, is the principal investigator for the project.

The study will focus on two genes, the leucine-rich repeat kinase 2 (LRRK2) and the serum glucocorticoid-regulated kinase 1 (SGK1). Genetic testing of several thousand Parkinson's patients has shown that the risk of Parkinson's disease associated with mutations in the LRRK2 gene are substantially reduced by mutations in the SGK1 genes, bringing the risk back in line with that of the general population.

"As a kinase, LRRK2 is the kind of molecule that drugmakers have a great deal of experience targeting. And as a significant genetic contributor to Parkinson's disease, it provides important therapeutic avenues for understanding the biological mechanisms and clinical aspects of PD," said Todd Sherer, PhD, CEO of The Michael J. Fox Foundation. "Dr. LoGrasso's expertise in kinases and his well known work in developing novel treatments for Parkinson's disease will be a particularly valuable addition to the promising research already being carried out with funding from the Foundation."

SGK1 was discovered by 23andMe, Inc., a leading personal genetics company. The company currently has 125,000 genotyped customers, and nearly 90 percent have opted-in to participate in the company's Institutional Review Board-approved research. 23andMe has amassed the single largest Parkinson's research cohort in the world, which now comprises approximately 6,000 participants and includes one of the largest cohorts of individuals carrying the pathogenic mutations in the LRRK2 gene.

With this award Dr. LoGrasso joins the LKRR2 Consortium, established last year by the Michael J. Fox Foundation. The consortium is an international group of academic and industry partners dedicated to accelerating LRRK2 therapeutic development.

"I want to thank the Fox Foundation for their generous grant," LoGrasso said, "and for giving me the opportunity to study the links between these intriguing genetic mutations. The question our laboratory will explore is how SGK1 works and how it impacts the LRRK2 mutation. We're all hoping that ultimately this produces a new target for treatment intervention because there are no viable long-term treatments available today."

Since the 1960s the mainstay for the treatment of Parkinson's disease has been levodopa (L-DOPA), a drug that provides only symptomatic relief. Unfortunately, L-DOPA loses efficacy over time and has numerous side effects that limit its effectiveness.

Patients with Parkinson's disease suffer from a loss of dopaminergic neurons in a specific area of the brain. An estimated one million Americans are believed to suffer from the disease, according to the Parkinson's Disease Foundation; approximately 40,000 new cases are reported annually.

The LRRK2 gene was first linked to Parkinson's disease in 2004, and many believe it to be the most common genetic contributing factor to the disease. While hereditary forms of the disease are relatively rare an estimated five to 10 percent unlocking the mechanisms involved in both LRRK2 and SGK1 could eventually benefit all patients.

Mutations in the LRRK2 gene have been linked with an increased risk not only of Parkinson's disease, but also of Crohn's disease. SGK1 is involved in a number of biomolecular processes including inflammation, cell proliferation, and apoptosis or programmed cell death. It is believed that the gene also plays a role in brain disorders other than Parkinson's disease, such as schizophrenia, depression, and Alzheimer's disease.


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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert

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