A ‘Milestone Moment’ for Parkinson’s: LRRK2 drug moves to next stage
Monday, 29th October 2018

“Forbes” recently published a story detailing a “milestone moment” in the history of LRRK2 and the linchpin role of The Michael J. Fox Foundation (MJFF) in ushering this promising genetic target forward.

The LRRK2 gene was discovered in 2004, leucine-rich repeat kinase 2 (LRRK2) and is the greatest known genetic contributor to Parkinson’s disease (PD).

In order to streamline and orchestrate drug development around the gene The Michael J. Fox Foundation (MJFF) pioneered an innovative approach to LRRK2 by forming the LRRK2 Consortium to test critical hypotheses about both normal and pathological LRRK2. This collaborative network of more than 30 investigator teams aimed to help researchers understand LRRK2’s structure and function in order to identify drug candidates that can modify its activity in the body and the brain.

A few years ago, after researchers published preclinical findings showing a LRRK2 inhibitor led to changes in lung tissue, the LRRK2 target was nearly stalled. Then, “the Fox Foundation stepped in.” MJFF brought together three competing companies developing LRRK2 drugs for Parkinson’s through the LRRK2 Safety Initiative. The Initiative demonstrated that LRRK2 inhibitors were safe for human testing, allowing continued investment and research. This industry consortium, coupled with preclinical funding from The Michael J. Fox Foundation, ensured the next phase of LRRK2 drug development could advance.

Fast forward to today and a milestone moment for Parkinson’s with a trial of the LRKK2 drug moving to the next phase of development. Denali Therapeutics — a San Francisco-based biotech — presented data from its Phase I LRRK2 trial to more than 300 Parkinson’s researchers and industry professionals at a recent conference. Denali’s Phase I study, which investigated the drug in healthy volunteers, sought to answer two important questions:

“Can the LRRK2 drug block the LRRK2 enough that it might work in Parkinson’s patients? Can it do so without serious side effects, particularly in the lungs, or related to blood pressure? The answer to both questions appears to be yes.”

The next step will be to test Denali’s LRRK2 drug in patients with Parkinson’s — both those whose disease is caused by a LRRK2 mutation and those whose Parkinson’s is not related to LRRK2.

MJFF Senior Vice President of Research Programs Brian Fiske, PhD, explained the significance of this new data:

“For us, it’s very exciting and promising to see that a LRRK2 inhibitor has entered human testing. Obviously, that’s the first step for testing people with Parkinson’s. This was kind of a milestone moment.”

Brian Fiske – Senior Vice President, Research Programs


Shake It Up continues to fund research in LRRK2 with several projects currently underway at the University of Sydney with Professor Glenda Halliday and Dr NIcholas Dzamko

Professor Halliday and Dr Dzamko share a message on the importance of research to step us closer to better treatments and a cure.