LRRK2 Investigative Therapeutics Exchange (LITE)

Program Details: LRRK2 is a gene that makes a protein that helps control different activities inside our cells, such as how they communicate and clean up waste. Mutations in the LRRK2 gene were first linked to Parkinson’s disease (PD) 20 years ago, and they are now understood to be the most common causes of inherited PD. The mutations are believed to hyperactivate LRRK2, triggering cellular dysfunction that leads to PD. Researchers are looking for strategies to reduce LRRK2 hyperactivity, which could help the 4 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 pharma and biotech 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 discovered initial hits and lead molecules that could be used as tool compounds by the research community or be advanced through partnerships with companies.  
• Developed new preclinical and clinical resources for use by partner companies and the broader research community.  For example, LITE will have established a cohort of LRRK2 mutation carriers from sites across the globe with associated biosamples for broader sharing.
• Tested potential new LRRK2 biomarkers to determine if they can serve as enrichment tools for future LRRK2 trials.  
• Set up infrastructure and a model to deploy this approach to other emerging PD targets.  

The LITE program is built on open-science policies and collaboration where data, preclinical resources and expertise will be shared across the Consortium. This approach will expedite and advance the pipeline while ensuring that outcomes follow scientific rigor and are reproducible.

The initiative will be governed by a steering committee consisting of Foundation staff and key advisors with drug discovery and LRRK2 biology expertise. It will be implemented by the University of Dundee in the United Kingdom with strong collaborations from more than 20 academic key opinion leaders, more than 20 biotech and pharma key opinion leaders and more than 10 clinical advisors.  

LITE will be led by Dario Alessi, PhD, who 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.  

Collaborative Initiatives: A related project focusing on LRRK2 signaling pathways is part of the Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network (CRN), creating a point of collaboration across initiatives. 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).    

Academic Collaborators Include:  

• Cincinnati Children's Hospital Medical Center — Dr. Jeffrey Whittset, Dr. William Zaccharias
• National University of Singapore — Dr. Ji Sun
• St Jude Children’s Research Hospital — Dr. Christoph Gorgulla
• SGC — Dr. Alison Axtman, Dr. Rafael Counago
• University of Toronto — Dr. Aled Edwards, Dr. Levon Halabelian
• Stanford University — Dr. Monther Abu-Remaileh, Dr. Nathaniel Gray
• Stanford University School of Medicine — Dr. Suzanne Pfeffer
• Trinity College Dublin — Dr. Amir Khan
• University of Dundee — Dr. Mahmood Ahmed, Dr. Alessio Ciulli, Dr. Will Farnaby, Dr. Peter Cossar   

Industry Collaborators Include: 1STBIO, Ambagon, Biogen, Brenig, Denali, GSK, Highlight, Montara, Neoclease, Neuron23, Novorex, Opprtna, Organo, Schrodinger 

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

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MJFF launches program to expedite development of LRRK2-targeted therapies and biomarkers for Parkinson’s disease