Combining Human Disease Genetics and Mouse Model Phenotypes towards Drug Repositioning for Parkinson's disease.

Parkinson's disease (PD) is a severe neurodegenerative disorder without effective treatments. Here, we present a novel drug repositioning approach to predict new drugs for PD leveraging both disease genetics and large amounts of mouse model phenotypes. First, we identified PD-specific mouse phenotypes using well-studied human disease genes. Then we searched all FDA-approved drugs for candidates that share similar mouse phenotype profiles with PD. We demonstrated the validity of our approach using drugs that have been approved for PD: 10 approved PD drugs were ranked within top 10% among 1197 candidates. In predicting novel PD drugs, our approach achieved a mean average precision of 0.24, which is significantly higher (p<e-11) than 0.16 for a state-of-art drug discovery approach based on mouse phenotype data. Comparison of gene expression profiles between PD and top-ranked drug candidates indicates that quetiapine has the potential to treat PD.