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 potential therapeutic target for Parkinson’s disease.
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,” says Todd Sherer, PhD, chief executive officer of The Michael J. Fox Foundation.
With this award, LoGrasso joins the LKRR2 Consortium, established in 2010 by the Michael J. Fox Foundation. The consortium is an international group of academic and industry partners dedicated to accelerating LRRK2 therapeutic development.
“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,” says LoGrasso.
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.
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, unlocking the mechanisms involved in both LRRK2 and SGK1 could eventually benefit 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. 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.
Release Date: Oct. 26, 2010
Source: The Scripps Research Institute