Data-driven identification of repurposable drugs for ALS
Abstract
Amyotrophic lateral sclerosis (ALS) is a severe disease that causes thousands of deaths annually. Current treatments are either limited in effectiveness or not broadly applicable. To discover new options, we conducted a genetics-based screen to identify drugs that could be repurposed for ALS. We analyzed genome-wide data from over 150,000 samples ( n = 29,612 ALS patients and 122,656 controls) to assess the ability of FDA-approved drugs ( n = 1001) to restore disease-related gene expression. Our findings were validated using U.S. Medicare prescription claims data from 114,950 participants across diverse populations. The screen identified furosemide , a diuretic used for hypertension and heart failure, as a promising candidate for further research. Clinical trial simulations using public data further supported the beneficial effects of furosemide , and ex vivo experiments in mice suggest the drug may protect neurons by reducing hyperexcitability. Our data-driven, multidisciplinary approach has broad potential for repurposing drugs to treat neurodegenerative diseases.