Amyotrophic lateral sclerosis (ALS) is an invariably fatal neurodegenerative disease with no effective treatments for the symptoms or therapies that modify the disease course. In this study, we will be using Medicare Part D medication data obtained from the Centers for Medicare and Medicaid to identify prescription medications associated with a lower risk of developing ALS. Within those medications associated with a lower risk of ALS, we will prioritize the top candidates and test these medications in an ALS mouse model system. This innovative proposal represents a new collaboration between two highly experienced Washington University School of Medicine researchers with unique but complementary expertise. The ultimate goal of this project is to identify prescription medications that can be repurposed to modify the disease course for this catastrophic neurodegenerative disease.