Study Rationale:
Parkinson's is a complex disease combining genetic, environmental and inflammatory causes. Mutations in the GBA gene are a leading genetic contributor to Parkinson's disease. While GBA mutation carriers are at an increased risk for developing PD, the impact of inflammation on disease presentation and onset has not been studied.
Hypothesis:
We expect to find higher inflammatory markers among people with Parkinson's and a GBA mutation compared with people with idiopathic (cause unknown) Parkinson's disease. We also expect higher inflammatory markers among non-manifesting carriers of GBA mutations, which we hypothesize will correlate with early disease symptoms.
Study Design:
We will perform a comprehensive assessment of patients and non-mutation carriers and analyze plasma for pro-inflammatory cytokines and levels of the protein GCase, which the GBA gene encodes. Parkinson's patients with GBA mutations will be compared to patients without mutations, while non-manifesting GBA mutation carriers will be compared to healthy non-carriers.
Impact on Diagnosis/Treatment of Parkinson's Disease:
If indeed GBA mutation carriers (with and without Parkinson's) have an elevated inflammatory profile, this could lead the way for anti-inflammatory treatments for this unique population, possibly improving disease symptoms and reducing the risk of developing Parkinson's among non-manifesting carriers.
Next Steps for Development:
We believe that our findings will open a new path for potential disease-modifying therapies and will improve our knowledge regarding interaction between genetics and inflammation among both patients and at-risk populations.