Funded Studies
Study Rationale:
Impaired mitochondria are a shared feature of Parkinson's disease (PD). Thus restoration of mitochondrial function offers a therapeutic avenue to slow the progression of PD. Parkin that plays a role in mitochondrial quality control and PD. Genetic mutations in parkin cause PD, and changes in parkin-related biology can be seen even in patients without parkin mutations. Increasing the amount of parkin has shown to be protective in several models of PD. With this evidence, we have embarked on a drug discovery effort to identify parkin activators.
Hypothesis:
Small molecule parkin activators can be optimized into therapeutic molecules to restore mitochondrial function in cells and disease models.
Study Design:
We will test parkin activity and drug-like properties to identify novel parkin activators as therapeutic candidates. Initial studies will be in test tubes, followed by in cells, to identify compounds with desired levels of parkin activation. These compounds will be tested and modified, as needed, to introduce drug-like properties. In the final step, we will test a small number of compounds in laboratory models to demonstrate parkin activation and improvement in mitochondrial function. These compounds will be candidates for further therapeutic development.
Impact on Diagnosis/Treatment of Parkinson's Disease:
Laboratory data suggest that increasing parkin may block the loss of neurons in Parkinson's disease. If successful, this project will deliver new proprietary molecules that can be developed further as therapeutics to slow the progression of Parkinson's disease.
Next Steps for Development:
The next step is to conduct further tests on the compounds to demonstrate their safety and suitability for human testing and seek regulatory approval for the clinical testing.