Skip to main content
Funded Studies

Developing an Assay to Identify Glucocerebrosidase-enhancing Chaperones for the Treatment of Parkinson’s Disease

Study Rationale: Discovering genes associated with Parkinson’s disease (PD) facilitates the design of new treatment strategies for this disorder. Mutations in the glucocerebrosidase gene (GBA1) are the most common genetic risk factor for Parkinson disease. GBA1 mutations lead to a shortage of glucocerebrosidase, an enzyme that operates in lysosomes, cell compartments responsible for breaking down waste products. We are working on creating tools that will allow us to develop drugs that increase glucocerebrosidase specifically in lysosomes. Such tools are not currently available. Boosting glucocerebrosidase may prevent the toxic accumulation of the protein alpha-synuclein, a key event in the pathology of PD.

Hypothesis: We hypothesize that an assay for measuring glucocerebrosidase activity specifically in lysosomes will facilitate the identification of small molecules that can act as “chaperones” to help deliver glucocerebrosidase to this cell compartment, where the enzyme can degrade alpha-synuclein and potentially prevent PD.

Study Design: We are working on two new strategies to detect glucocerebrosidase activity in the lysosome. These assays will be tested in neurons that we generate by engineering skin cells collected from people with PD who have mutations in GBA1. We will then use these tools to identify and improve candidate small molecule drugs that increase glucocerebrosidase activity and prevent the accumulation of alpha-synuclein. The best candidates can be tested as a treatment for PD.

Impact on Diagnosis/Treatment of Parkinson’s disease: Identification of small molecules that guide glucocerebrosidase to the lysosome is a therapeutic strategy now under consideration for PD. The assays we develop and small molecules we identify will be critical for drug discovery and development and can be used by any laboratory investigating this treatment strategy.

Next Steps for Development: Using our new assays to successfully identify and confirm promising small molecules will facilitate their preclinical refinement and allow the generation of new small molecule drugs for PD that can ultimately progress to the clinic for testing.


  • Ellen Sidransky, MD

    Bethesda, MD United States

  • David Vocadlo, PhD

    Burnaby BC Canada

Discover More Grants

Search by Related Keywords

Within the Same Program

Within the Same Funding Year

We use cookies to ensure that you get the best experience. By continuing to use this website, you indicate that you have read our Terms of Service and Privacy Policy.