Funded Studies
Objective/Rationale:
We aim to develop a novel screening platform to identify candidate drugs to treat Parkinson’s disease. The screening platform incorporates the link between alpha-synuclein and GBA, the Gaucher’s Disease gene. Recent genetic and biochemical data suggest that this link could play a role in the development of Parkinson’s disease. Novel drugs that interfere with this link could thus have show potential as future disease-modifying therapies.
Project Description:
Recent discoveries have highlighted a link between Parkinson’s disease and the gene that can cause Gaucher’s Disease, GBA. It is clear that carriers of the Gaucher’s disease variant, who do not develop Gaucher’s, have a higher chance of developing Parkinson’s disease. Biochemical data suggests that alpha-synuclein, the protein that accumulates in Lewy bodies in the brain of Parkinson’s patients, affects the function of GBA, and loss of GBA function affects the levels of alpha-synuclein.
The screening platform that we aim to develop would interrogate the presence and localization of these proteins simultaneously, including additional parameters by automated high-throughput microscopy. With such an assay, large libraries of compounds can be screened in the future, to identify starting points for drugs with a new mode of action.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
This project has the potential to provide a platform which many researchers and drug discovery organizations can access and thereby help translate what we know about the alpha-synuclein-GBA link into ideas and molecules that will support the development of future drugs which could halt or slow the progression of Parkinson’s disease.
Anticipated Outcome:
Our project has the potential to inform us further about the biological significance of the link between alpha-synuclein and glucocerebrosidase in a range of cell systems including PD patient–derived cells. Furthermore, this study has the potential to impact the work of many researchers and drug discoverers through provision of a quantitative assay system which can been screened for new candidate drugs for PD.