Studying GBA Pseudogene as a Controller of GBA and Alpha-synuclein

Study Rationale: 
Mutations (changes) in the GBA gene are the most common genetic risk factor for Parkinson’s disease (PD). GBA has a clone called pseudogene, a similar stretch of DNA that, unlike the regular gene, does not play a role in producing the corresponding protein. It was recently suggested that GBA pseudogene may, in fact, control the function of GBA. This newly discovered ability may make the pseudogene a target for future drug development.

Hypothesis:
We hypothesize that the GBA pseudogene, through affecting GBA function, may also affect cellular buildup of alpha-synuclein, a sticky protein that clumps in the brains of people with PD.

Study Design:
We will generate stem cells and then nerve cells from cells donated by people with Parkinson’s disease with and without mutations in GBA. We will then use these nerve cells to determine whether the pseudogene affects the function of GBA and whether manipulating the pseudogene may affect GBA and the buildup of alpha-synuclein.

Impact on Diagnosis/Treatment of Parkinson’s disease:
If the GBA pseudogene can indeed affect the function of the GBA gene and the buildup of alpha-synuclein, the pseudogene would become a novel therapeutic target for PD.

Next Steps for Development:
If this study is successful, the next step would be to determine what controls the pseudogene (e.g., miRs, transcription factors or other factors) and to accomplish therapeutic effect by manipulating those factors.