Progress Report
Study Rationale: It is reported that over half of the people who live with Parkinson's for more than 10 years will develop dementia. A subset of these rapidly develop Parkinson’s disease related dementia complex (PDD) with devastating cognitive decline and hallucinations. There are currently no treatments to slow or stop the brain cell damage caused by Parkinson’s disease dementia so this is an unmet medical need.
Hypothesis: We propose to halt or reverse the accumulation of aggregated protein that leads to Parkinson’s disease related dementia. Genetic variants of a gene called APOE encoding a lipid carrier protein have a huge impact of the risk for PDD with the APOE4 variant providing very high risk and the APOE2 variant being protective. We hypothesize that delivery of APOE2Ch by gene therapy vector will stem the progression of PDD.
Study Design: The program will use a mouse model of Parkinson’s disease to determine if this method is effective in slowing or even reversing the development of Parkinson’s disease related dementia. The first study is a prevention experiment where young mice will get a one-time gene therapy treatment to see if this slows or stops the pathology they would otherwise develop. Then we will assess mice in a treatment scenario with older mice who already have some pathology and see if we can preserve cognition and performance relative to untreated controls.
Impact on Diagnosis/Treatment of Parkinson’s disease: As with any experimental therapy, the outcome is uncertain. However, our work on using this approach to prevent progression of pathology in mouse models of Alzheimer’s disease provides cause for optimism. A successful program would provide a drug that is a one-time treatment for mild cognitive decline in Parkinson’s patients that slows or stops further progression.
Next Steps for Development: In coordination with The Micheal J. Fox Foundation and stakeholders, successful completion of the goals would trigger a preclinical program. Following FDA guidance, additional steps towards clinical assessment would begin. These include further proof of concept (if needed), clinical grade drug manufacturing and demonstration of safety in animals and design of a clinical trial.