Study Rationale:
Neurodegeneration in the brains of people with Parkinson’s may be caused by protein clumps called Lewy bodies, the pathological hallmark of the disease. Lewy bodies consist of a protein called alpha-synuclein, which is encoded by the SNCA gene. The normal function of this protein is still unclear, but studies show that a surplus of alpha-synuclein can be the root cause of neurodegeneration.
Hypothesis:
We hypothesize that lowering the alpha-synuclein clumping through novel gene therapy will reduce its toxic effects thus reversing or preventing Parkinson’s.
Study Design:
In this study, we are aiming to lower alpha-synuclein protein levels by modifying SNCA gene to decrease the gene’s expression. This gene therapy uses a gene-engineering technology called CRISPR that allow scientists to alter a particular location in the genome. The CRISPR system penetrates the cells through a safe delivery system and will only change the expression of the SNCA gene and impact alpha-synuclein protein production. This approach has been tested on neuronal cells derived from induced pluripotent stem cells, and this study will optimize delivery and the design of the CRISPR system in pre-clinical models of tParkinson’s disease and assess the long-term effects of this therapy.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
Reducing the expression of the SNCA gene in brain cells through our gene therapy holds the potential to slow the progression or halt the disease process of Parkinson’s disease by decreasing abnormal levels of alpha-synuclein protein.
Next Steps for Development:
Ultimately, the outcome of the pre-clinical studies is the optimization of this gene therapy for regulatory approval in clinical trials.