Mutations (changes) in the LRRK2 gene are a leading genetic cause of Parkinson's disease (PD) and cause dysfunction in the LRRK2 protein. However, not all LRRK2 mutations cause the disease. Because some mutations have not yet been confirmed to cause Parkinson's, the number of people with LRRK2-associated PD is likely underestimated. As therapeutics targeting LRRK2 are being developed, it is important to accurately identify people who might benefit from them.
We hypothesize that some rare LRRK2 mutations identified in the Parkinson's Progression Markers Initiative (PPMI) study cause Parkinson's disease just as well-known LRRK2 mutations do. PPMI is The Michael J. Fox Foundation's landmark clinical study to find biomarkers -- disease indicators that are critical missing links in the search for better Parkinson's treatments.
We have identified four LRRK2 mutations in the PPMI data. We will compare the effects of these mutations on the function of the LRRK2 protein with the effects of mutations known to cause the disease. We aim to determine whether these new mutations cause the disease.
Impact on Diagnosis/Treatment of Parkinson's Disease:
Confirming the ability of these mutations to cause PD will identify more individuals who might benefit from LRRK2-targeting therapies and, as a result, speed the development of those therapies.
Next Steps for Development:
If this study is successful, we will launch large-scale, multi-center clinical studies to identify people with Parkinson's caused by new mutations, as well as gather family histories from these people. We will also aim to identify biomarkers -- measures of LRRK2 dysfunction -- in biofluids of people with and without PD.