Funded Studies
Study Rationale:
Mutations that disable glucocerebrosidase (GBA), a protein that strips sugars from molecules in the membranes of brain cells, are associated with Parkinson’s disease (PD). While pharmaceutical scientists work on developing drugs that boost GBA activity as a novel treatment for PD, we are developing probes for monitoring GBA activity in the brain using positron emission tomography (PET). Such imaging techniques could help us unravel how dysfunctional GBA promotes neurodegeneration, test drugs for their ability to boost GBA, and identify people with PD who would benefit from GBA-enhancing drugs.
Hypothesis:
Our hypothesis is that the promising GBA-imaging probes already discovered by our team can be enhanced to produce the next-generation of candidates for evaluation in pre-clinical models of Parkinson’s disease, thus enabling us to obtain the data needed to move toward future human studies.
Study Design:
To generate PET scans that reveal GBA activity, subjects are injected with a tiny amount of a radioactive probe that enters the brain and latches onto GBA. We will produce next-generation probe candidates with improved performance for testing in pre-clinical models of PD, and using our well-designed pre-clinical screening platform, we will identify the best candidates for future human studies. We will also map out the levels of GBA activity in donor tissue samples and compare GBA activity in different brain regions in both control and PD brains, which will help us understand the role GBA plays in neurodegeneration.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
Tools that provide images representing the activity of GBA in the living brain would help to identify the best GBA-boosting therapies, track treatment responses, and select patients best suited for clinical trials. All of these outcomes will help researchers develop new and improved drugs for Parkinson’s disease.
Next Steps for Development:
If we are successful in discovering probes that can detect GBA by PET imaging in pre-clinical models, we will seek additional industrial and academic partners and start the approval process for the first “in patient studies.” Further studies will provide validation that PET scans can be used to image GBA in people with PD.