LRRK2 Investigative Therapeutics Exchange (LITE)

Program Details: LRRK2 is a gene that makes a protein that helps control different activities inside our cells, like how they communicate and clean up waste. Mutations in the LRRK2 gene were first linked to PD 20 years ago, and they are now understood to be the most common causes of inherited PD. The mutations hyperactivate LRRK2, triggering cellular dysfunction that leads to PD. Researchers are looking for strategies to reduce LRRK2 hyperactivity, which would help the four percent of people with inherited LRRK2 mutations. Research also suggests LRRK2 therapies could have much broader use, helping people without mutations as well. 

The LITE program will pave the way for new approaches to target LRRK2, connect companies that are developing LRRK2-targeting therapies with key opinion leaders, and provide preclinical and clinical resources to establish best practices for advancing LRRK2 therapeutics. LITE will establish infrastructure to test new LRRK2 biomarkers in individuals with and without PD. At the end of the 3-year funding period, we expect to:  

• Have tested more than a dozen strategies for targeting LRRK2 and have initial hits and lead molecules that could be used as tool compounds by the research community or be advanced through partnerships with companies.  

• Have developed new preclinical and clinical resources for use by partner companies and the broader research community.  

• Have tested potential new LRRK2 biomarkers to determine if they can serve as enrichment tools for future LRRK2 trials.  

• Have set up infrastructure and a model to deploy this approach to other emerging PD targets. 

LITE will be led by Dario Alessi, PhD, a global leader in the study of kinases, a class of cellular proteins that includes LRRK2. Alessi, the winner of the 2023 Robert A. Pritzker Prize for Leadership in Parkinson’s Research, runs a lab focused on kinase research at the University of Dundee in the United Kingdom. Alessi’s colleague Esther Sammler, MD, PhD, will serve as co-principal investigator on the program. University of Dundee UK’s Paul Davies, PhD, and Francesca Tonelli, PhD, will join them as part of the study’s leadership. The study also receives key guidance from advisors Darryle Schoepp, PhD, and Alastair Reith, PhD. 

Collaborators: In addition to leading LITE, Alessi leads a project focusing on LRRK2 signaling pathways as part of the Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network (CRN), creating a point of collaboration across organizations as he continues to build on this work in the space. The LITE program also will benefit from collaboration with other ASAP initiative-supported programs including the Parkinson’s Progression Markers Initiatives (PPMI) and the Global Parkinson’s Genetics Program (GP2).   

If you have questions about the program or are interested in contributing, please contact: grants@michaeljfox.org