In the MJFF Winter 2011 newsletter, we highlight the Foundation's multi-pronged approach to speed progress around LRRK2, the most common genetic contributor to PD known to date.

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Since first being linked to Parkinson’s disease (PD) in 2004, the LRRK2 gene has become an increasingly important target for PD researchers across the globe — and for MJFF. It is now believed to be the most common genetic contributor to the disease in the general population.

With leadership funding from the Brin Wojcicki Foundation, The Michael J. Fox Foundation (MJFF) has invested more than $38 million in research projects devoted to LRRK2 to date, and has made the translation of this finding into meaningful therapeutics one of its key priority areas.

This fall, MJFF announced the expansion of the LRRK2 Cohort Consortium, a group of eight separate research teams funded by MJFF to bring together and learn from people with and without PD who carry mutations in the gene. The cohorts are made up of more than 3,000 people across 20 clinical sites worldwide. By building a large network of patients and their families, and compiling significant clinical data on LRRK2 parkinsonism over time, the Foundation hopes to lay the groundwork for effective LRRK2 clinical trials once appropriate drug candidates have been identified.

A global LRRK2 consortium takes shape

LRRK2 may play a particularly frequent role in cases of PD among certain populations, including Ashkenazi Jews, North African Berbers and Asians of Chinese descent. Yet a recent study by MJFF awardee Dr. Owen Ross suggests that we may have only begun to determine the significance of LRRK2 and its role in PD in other populations across the globe. Piloted in 2009 to assemble cohorts of Ashkenazi Jews in New York and Tel Aviv and North African Berbers in Tunisia, the LRRK2 Cohort Consortium today includes additional sites across the United States, Canada, China, Germany, France, Norway and Spain.

“One of our top priorities at MJFF is to find ways to alter the progression of PD. By studying individuals with the LRRK2 mutation, we hope to learn more about why certain populations are susceptible to the disease,” said Brian Fiske, PhD, director of research programs at MJFF. “By investigating how this mutation works in people with PD, we also can find out more about Parkinson’s on the whole, accelerating development of therapies that will benefit everyone with the disease, not just those with mutations in LRRK2.”

Scientists in the Consortium will share clinical data, housed at a central repository at the University of Rochester in Rochester, New York. MJFF will coordinate the standardized collection of various biosamples from individuals with LRRK2 mutations, and make them available to the research community at large.

Initial findings from Consortium studies to date already have prompted MJFF to establish working groups to validate results related to issues including posture and gait disturbances, a LRRK2-cancer link, and impaired sense of smell as a pre-diagnostic biomarker for LRRK2-related PD.

A multi-pronged approach to speed progress

The Consortium is one element of the Foundation’s multi-pronged approach to speeding development of LRRK2-based treatments for PD. MJFF is also funding and coordinating the LRRK2 Biology Consortium, a collaborative network of more than 30 investigator teams studying LRRK2’s structure and function to advance development of practical treatment strategies. And MJFF’s staff scientists are spearheading the creation and distribution of high-quality LRRK2 pre-clinical models, essential and traditionally elusive tools for high-impact research, for distribution at low cost to industry and academic labs starting in 2012.

LRRK2 and Industry

Pharmaceutical companies are interested in developing drugs to target LRRK2. It is a type of protein called a kinase, which, in PD, is believed to result in overactivity. Drugmakers have amassed extensive experience, primarily from cancer research, developing so-called kinase inhibitors, which can counter this molecular overactivity. There are not yet specific drugs in clinical testing to treat LRRK2 parkinsonism, but drug companies are actively pursuing research that could lead to potential therapies.

To this end, MJFF has also established a LRRK2 Industry Advisory Group, including representatives from Pfizer, Elan, Sanofi-aventis, Eli Lilly, MerckSerono, GlaxoSmith Kline, and others. The group’s goal is to ensure that LRRK2 therapeutic development is executed in a way that ultimately yields the most efficient results for patients. Members of the group come together in a precompetitive space to discuss how to best create and share resources that will most effectively push LRRK2-based drugs closer to the clinic.

Says Advisory Group member Alastair Reith, PhD, of GlaxoSmithKline: “MJFF’s LRRK2 strategy allows for a unique approach where academia provides breakthrough science, industry provides capabilities for drug discovery and testing, and MJFF provides necessary disease focus to drive both forward.”