This grant builds upon the research from a prior grant: Pre-clinical Safety Study of LRRK2 Inhibitors
Previous pre-clinical work with Genentech, Inc. has demonstrated that LRRK2 kinase inhibitors may induce abnormal findings in the lungs. This study will determine if this result is due to those specific compounds or if targeting LRRK2 is a safety liability.
Is inhibition of LRRK2 safe in pre-clinical models?
Several potent and selective LRRK2 kinase inhibitors from different pharmaceutical companies will be chronically dosed in a pre-clinical model and peripheral organs, especially the lungs, will be evaluated for any abnormalities.
Impact on Diagnosis/Treatment of Parkinson's disease:
These exploratory toxicity studies will be crucial in determining if LRRK2 kinase inhibitors are viable therapeutics to be tested in humans.
Next Steps for Development:
A negative toxicity finding will allow for further development of LRRK2 kinase inhibitors in the clinic. If we confirm that multiple LRRK2 kinase inhibitors are a safety liability, we will follow up with more studies to understand the mechanism of action.