Study Rationale:
The protein parkin plays a critical role in the health and maintenance of the brain cells that make dopamine, which degenerate in Parkinson's disease. Scientific evidence shows that restoring parkin activity can restore dopamine cell function and slow cell loss. We have made small molecule drug candidates that activate parkin and plan to test if they alter progression of Parkinson's disease.
Hypothesis:
Parkin-activating compounds can ease dysfunction caused by an impaired cellular response in a new model that mimics a defect observed in Parkinson's disease.
Study Design:
Our study will test parkin compounds in a laboratory model designed to reflect the dopamine cell damage seen in people with Parkinson's and impaired parkin pathway activity. We will analyze the cellular response in models treated with the compound to predict whether our drugs may help people with Parkinson's disease. In addition, we will determine if a blood-based marker can be used to monitor efficacy with the therapy and identify patients likely to respond to our drug.
Impact on Diagnosis/Treatment of Parkinson's Disease:
Parkin-targeting therapies may be a treatment to help slow or stop Parkinson's progression. In addition to furthering development of such drugs, this project may validate a parkin biological marker to select participants for studies and measure therapeutic efficacy.
Next Steps for Development:
Should this study be successful, there are two key next steps. We will expand our chemistry efforts to synthesize more compounds with optimized properties and test drug candidates for safety in Parkinson's models.