Objective/Rationale:
We are targeting a molecule, for the first time in Parkinson’s research, that is only present in the human brain’s motor circuitry and that we believe will respond to a new pharmacological therapy. We believe this new approach will treat the motor symptoms of Parkinson’s disease (PD) without leading to the side effects that patients are currently experiencing with dopamine-replacing agents.
Project Description:
We have recently discovered multiple small molecules that are capable of inhibiting the activity of a protein that is likely to play a critical role in controlling movement. The protein has not been targeted before, and this project aims to demonstrate that inhibiting this protein with these small molecules reverses the motor symptoms in experimental models of PD and prevents the occurrence of the dyskinesia that frequently arise with current treatment paradigms. At a later stage we also plan to investigate the potential of the molecules to improve the cognitive deficiencies that some Parkinson’s patients experience. In parallel with our studies of the potential of these molecules for the treatment of PD, we will focus heavily on improving the drug-like properties of these compounds so that clinical trials of this novel treatment principle may be initiated at the earliest possible time.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
A novel medicine for PD not targeting the dopamine system of the brain could improve patient’s quality of life. Not only would such a medicine potentially be without dopamine-associated side effects such as dyskinesia, it could potentially surpass or supplement some of the existing treatment paradigms. By targeting a crucial protein in the brain’s motor circuitry, we rationalize that we will achieve exactly this and thereby making a life with Parkinson’s disease less difficult.
Anticipated Outcome:
We expect to validate a novel pharmaceutical target for the treatment of PD and develop an optimal starting point for creating a new medicine in the shortest possible time frame.