Searching for the Cause of Parkinson’s Disease in People with GBA Mutations

Study Rationale:
The GBA gene is responsible for the production of beta-glucocerebrosidase, an enzyme that breaks down fats. Scientists are starting to recognize changes, or mutations, in the GBA gene as a previously unknown cause of some Parkinson’s disease (PD) cases. Many healthy people also have a mutation in this gene but do not go on to develop PD. Mutations in this gene that make the enzyme completely dysfunctional also can cause Gaucher’s disease.

Hypothesis:
Within the scope of this planning project, we will set the stage for a large, international, collaborative study to identify specific features of the cell’s genetic material that determine whether GBA mutations lead to PD.

Study Design:
During the planning stage, we will identify suitable people and biobanks -- collections of biosamples -- to participate in this study. We also will prepare to work with clinics treating individuals with Gaucher’s disease. Our aim is to identify people with a GBA mutation who may be willing to participate in the study. Based on the information gathered and the number of people projected to enroll in the study, we will prepare a detailed research plan.

Impact on Diagnosis/Treatment of Parkinson’s disease:
Knowing the exact DNA features that determine whether Parkinson’s manifests in people with GBA mutations could be valuable in developing new PD therapies.

Next Steps for Development:
After successfully completing this preparatory work, we will conduct a large study to identify specific features of DNA that determine whether GBA mutations cause Parkinson’s disease.