PICALM Gene Therapy and Drug Screening for Abeta Clearance

2015, 2016

Our novel theory regarding PICALM, published last year in Nature Neuroscience, is that its genome-wide association study (GWAS)-linked impact on lower Alzheimer’s disease (AD) risk is due to its role internalizing Abeta into brain endothelial cells and then out into the bloodstream, effectively increasing amyloid clearance across the blood-brain barrier. We hope to increase PICALM expression to improve amyloid clearance by using an adeno-associated virus (AAV) as a vehicle to deliver gene therapy to increase endothelial expression of PICALM or, alternatively, by using a drug already safety-approved by the FDA retested and shown to have this effect. We will test both the gene therapy and the top drug hits in vivo for both amyloid load and rescue of behavioral deficits. Therapeutic strategies that upregulate PICALM expression in the overall brain vasculature could lead to rapid advancements in AD treatment.

Funding to Date



Drug Discovery, Drug Screening Projects


Berislav Zlokovic, M.D., Ph.D.

Beverly L. Davidson, Ph.D.