Fen Yang

Neurodegenerative diseases (NDDs) represent an escalating global health burden, yet effective disease-modifying therapies remain elusive. Drug repurposing offers a promising therapeutic strategy, but current efforts are often fragmented and lack reproducibility due to the absence of a unified framework that integrates real-world data with molecular evidence. This project aims to develop such a framework by combining clinical and bioinformatic approaches to accelerate the discovery of precision therapies for major NDDs, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis.Over three years, the research will proceed in three phases. First, we will conduct nested case–control studies using large-scale electronic health records from Sweden and the United States to identify associations between prescribed drug use and NDD risk. Second, we will strengthen causal inference through triangulation strategies, including family-based designs, target trial emulation, and drug-target Mendelian randomization. Third, we will employ molecular target mapping, including differential expression analysis and network proximity methods, to prioritize drug targets most likely to modulate key disease pathways.This integrative approach will generate robust, reproducible evidence for drug repurposing candidates, inform the design of future clinical trials, and support the development of effective therapies for NDDs.