Attend any Parkinson’s science meeting and you’ll hear it pronounced all ways. You’ll also hear about the growing list of therapies tied to the LRRK2 Parkinson’s pathway. [Keep scrolling for a list of recruiting studies.]

The Michael J. Fox Foundation (MJFF) advances understanding of Parkinson’s through initiatives around targets like LRRK2. This work helps us better define the disease, speed the most promising therapies, and connect people with the right clinical trials.

Remind me, what is LRRK2?

LRRK2 is a gene that we all carry. Some mutations (changes) in the gene are linked to a higher risk of Parkinson’s disease (PD). About 2 percent of all people with PD carry a LRRK2 gene mutation. These mutations cause overactivity in the LRRK2 protein pathway. Scientists think lowering that activity could protect cells and slow Parkinson’s progression.

Why am I still reading this post if I'm not in that 2 percent?

Don’t leave quite yet. People with Parkinson’s without a rare LRRK2 gene mutation may still have too much activity in the LRRK2 pathway. Other gene changes in or near the LRRK2 gene may also impact its function. Stopping that overactivity could be a way to treat the disease. 

Think of it as driving separately to meet a friend. You both leave your own homes, but your paths may merge to end up at the same spot. In the case of disease, there could be different causes that act on the same “highway” to reach Parkinson’s. 

I don't know if I have the LRRK2 gene change. How do I find out?

Many studies and services offer genetic testing and counseling. If you do have a LRRK2 variant, you can help scientists learn more about disease. A handful of studies are asking volunteers like you to have tests and share samples like blood or saliva. Findings from those studies could teach more about disease — and how to stop it.

Let's get to the studies.

New studies are enrolling people with and without a LRRK2 gene variant. MJFF also offers guidance on what to consider when choosing a research study. Speak to your Parkinson’s doctor if you are interested in these or other studies.

Observational Studies

In observational studies, you may have tests or scans and give samples such as blood. This helps scientists learn how disease starts and changes, which helps develop new therapies. You will not test a new treatment in these studies.

• MJFF’s landmark study, the Parkinson’s Progression Markers Initiative (PPMI), examines how disease starts and changes over time. Anyone over age 18 with or without Parkinson’s in the U.S. is eligible. Some people in other countries may be able to join too. PPMI is partnering with many people with LRRK2 gene changes and closely studying this disease connection.
• Scientists at Mt. Sinai Hospital in New York City also are studying the genetic causes of movement disorders. They are recruiting people with Parkinson’s and a known genetic cause (including a LRRK2 variant). The one-time study visit takes about an hour. Contact the research coordinator at abby.cohen@mountsinai.org.

Interventional Trials

Interventional trials test new treatments. You take therapy, have tests, and give samples. Scientists closely watch for side effects and study how the treatment impacts disease. Screening is now open for two trials: one for people with the LRRK2 mutation and one for anyone with Parkinson’s. Both are testing therapies that may slow or stop Parkinson’s progression.

• Denali Therapeutics is testing a drug to lower LRRK2 activity in people with a known LRRK2 gene change. This 12-week trial is enrolling participants at sites around the U.S. Anyone with Parkinson’s and a LRRK2 mutation may be eligible.
• Neuron23 has a genetic test to detect higher LRRK2 pathway activity in anyone with PD. Their data shows that 30% of patients, including people with no family history, may have this LRRK2-driven disease. The company is recruiting people not yet on dopamine medications to take their genetic test. People who test positive for LRRK2-driven disease (including those with the LRRK2 mutation) may be eligible to join NEULARK, a 12-month trial of a LRRK2 activity-lowering drug. This personalized medicine approach means participants may be more likely to respond to the treatment. 

What’s it like to be in a study? Hear from people who have raised their hands for research studies like these.