Study Rationale:
Abelson tyrosine kinase (c-Abl) is believed to drive the deleterious events leading to loss of dopamine neurons in people with Parkinson's disease. This project will identify small molecule inhibitors of c-Abl to suppress progression of Parkinson's disease.
Hypothesis:
Inhibition of c-Abl is neuroprotective in pre-clinical models of Parkinson's disease.
Study Design:
We will use three pre-clinical models that recapitulate hallmarks of Parkinson's disease to demonstrate that c-Abl inhibition is an effective treatment. This approach includes a model for sporadic disease associated with the majority of Parkinson's cases and a model representative of inherited disease. In each case, the efficacy of a c-Abl-inhibiting drug will be evaluated to demonstrate the likelihood of therapeutic benefit in human patients.
Impact on Diagnosis/Treatment of Parkinson's Disease:
c-Abl is a clinically validated target for drug treatment in patients, and has most commonly been used to suppress certain forms of stomach or blood cancer. Successful demonstration that the company's inhibitors are effective in models of Parkinson's will provide confidence that this can be recapitulated in people.
Next Steps for Development:
If this project rationalizes human treatment of Parkinson's with these c-Abl inhibitors, we will pursue regulatory approval to begin the process of evaluation of treatment benefit in people with Parkinson's disease.