LRRK2 Therapies May Be Useful for Wider Population

Parkinson's research

New research findings show a role for the LRRK2 protein in Parkinson’s disease among people without a LRRK2 genetic mutation. These results mean that drugs in development targeting LRRK2 might also benefit people without the mutation.

Researchers study genetic mutations linked to Parkinson’s to understand the causes of the disease and develop potential treatments. Human trials are already testing therapies designed to tackle the effects of mutations in the LRRK2 and GBA genes, for example. However, most people with Parkinson’s do not carry these mutations, which raises the question of whether these therapies will work for others with the disease.

The new findings — from a study funded by The Michael J. Fox Foundation (MJFF) — suggest that they might. In a paper published in the journal Science Translational Medicine, researchers reported activity of the LRRK2 protein was enhanced in dopamine neurons in people with idiopathic (i.e., unknown cause) Parkinson’s and in laboratory models of the disease.

“Our work suggests that the LRRK2-targeted treatments that are being developed for the three percent of Parkinson’s patients with LRRK2 mutations may be useful for people without mutations. It’s an exciting time for those affected by Parkinson’s; disease-modifying therapies are on the horizon,” said lead author J. Timothy Greenamyre, MD, PhD, of the Pittsburgh Institute for Neurodegenerative Diseases and the University of Pittsburgh.

Companies are developing drugs to lower LRRK2 protein activity after an MJFF-led group showed it was safe to test this type of therapy in humans. Read about one such drug in human trials.

Plotting Biology and Identifying Biomarkers
Greenamyre is building on these results to better understand what causes too much LRRK2 activity, including investigating the role of environmental toxins. That project is funded by MJFF through our PATH to PD program to better understand how Parkinson’s disease starts.

“We are looking into the molecular mechanisms of how the normal LRRK2 protein gets hyper-activated, and we are trying to develop a simple, blood-based test (i.e., a biomarker) that might be useful for diagnosis or for testing whether therapies targeting LRRK2 are actually doing what we hope they are,” he said. “The work is progressing nicely, thanks in part to funding from The Michael J. Fox Foundation.”

Pursuing More Links to LRRK2
Our Foundation is supporting a number of other projects investigating the connection between LRRK2 and idiopathic Parkinson’s disease. For example, scientists at the National Institutes of Health are using engineered stem cells to investigate that link.

In another project, an MJFF-organized group of scientists from around the world are measuring Rab proteins — which are regulated by LRRK2 — to see if they could develop a test for LRRK2 activity and therapeutic impact in both people with LRRK2 mutations and those with idiopathic Parkinson’s disease.