This grant builds upon the research from a prior grant: Functional Evaluation of Alpha-synuclein Dosage Effects in CRISPR‐edited SNCA Model
Study Rationale: Numerous genetic studies of families with parkinsonism and mutations in the alpha-synuclein gene suggest that an excess of alpha-synuclein leads to neurodegeneration and Parkinson’s disease (PD). We propose to develop a gene therapy system that will allow us to reduce the activity of the alpha-synuclein gene in an advanced preclinical model of PD. This approach should limit the buildup of alpha-synuclein, with the goal of stopping or slowing the neurodegenerative process in PD.
Hypothesis: We hypothesize that limiting the expression of the alpha-synuclein gene will diminish alpha-synuclein accumulation and, ultimately, slow neurodegeneration.
Study Design: We propose using an advanced preclinical model to examine how our gene therapy product gets distributed in the brain and peripheral organs. We will also test different ways to deliver the gene therapy and peripheral organs and assess how the immune system responds to the treatment.
Impact on Diagnosis/Treatment of Parkinson’s disease: For gene therapy to be developed as a successful treatment for slowing disease progression, we must determine the optimal mechanism for safely delivering the therapy to all relevant brain regions affected in PD.
Next Steps for Development: These studies are critical for the clinical development of this gene therapy toward regulatory approval and first-in-human clinical trials.