Parkinson's disease affects millions worldwide, and while current treatments address symptoms, none slow or stop the disease. The discovery of a gene pathway that contributes to Parkinson's risk has opened up a promising new avenue for developing therapies. Treatments that act on this pathway are now being tested in clinics. As part of an initiative to address gaps in our understanding of this pathway, and to ensure success in trials, more than 80 experts convened in June 2025 to create a roadmap for accelerating therapies.
Mutations in genes affecting this pathway, known as leucine-rich repeat kinase 2, or LRRK2, account for around 1 or 2 percent of all Parkinson's cases. In some populations, though, they account for up to 40 percent of cases, making this the most common genetic cause of Parkinson's. Pathogenic variants in LRRK2 amplify the activity of a type of enzyme known as a kinase, disrupting cellular mechanisms, leading to Parkinson's. Kinases have been well studied as drug targets in other diseases, and partially blocking the LRRK2 pathway appears safe in humans. Growing evidence suggests this pathway also has a role in Parkinson's among a subset of patients who don't have the same genetic mutations. They have similar LRRK2 pathway dysfunction (“LRRK2-like” cases) and could benefit from the same therapies. That makes this one of the most promising routes toward treating Parkinson's.
Yet several challenges remain. One is just getting enough people for clinical trials. These variants are relatively rare, and not all carriers develop Parkinson's. Including people with LRRK2 pathway dysfunction but no mutation would expand the population for clinical trials, but there is no validated way to identify them.
These challenges complicate trial design for testing new therapeutics. Should studies focus only on those who carry the pathogenic mutation (which may be the most biologically justified but would make it harder to recruit)? Should they broaden to the LRRK2-like cases (who would be hard to identify)? Or should they include all Parkinson's cases and identify carriers of the LRRK2 mutation afterward (which could make it harder to track the efficacy of any treatments)?
Including people with LRRK2 pathway dysfunction but no mutation would expand the population for clinical trials, but there is no validated way to identify them.
The Michael J. Fox Foundation launched the LRRK2 Investigative Therapeutics Exchange (LITE) initiative in 2024 to address these challenges. The initiative creates a collaborative, precompetitive space where industry leaders, academics, and regulators can share tools, data, and insights. The June 2025 convening brought together attendees to define priorities for the initiative. In the short term, those include building an inventory of all known cohorts with pathogenic LRRK2 mutations worldwide and validating biomarkers to identify them. Medium-term priorities include finding a way to identify those patients without the mutation who would likely still benefit from these therapies and designing innovative trials to accelerate testing. In the long term, these efforts could build to a system of precision medicine for some Parkinson's patients, including biomarker-guided treatment selection and predictive tools to identify carriers before the onset of disease.
Call to Action
Delivering a therapy that slows or prevents Parkinson's progression will require intentional and sustained collaboration across stakeholders. Industry leaders will need to collaborate to validate biomarkers and share data. Researchers can help by coordinating methods, sharing results, and investing in analyses across patient cohorts. Patients and communities also have a role to play, by participating in genetic testing and observational studies that make these therapies possible. Finally, funders and foundations should continue supporting these collaborations as they scale up.
This effort could serve as a model for how cross-sector collaboration can change the trajectory of neurodegenerative diseases. With shared purpose, we are moving toward precision medicine approaches that address some of the underlying causes of Parkinson's Disease, not just the symptoms.
