Neuroleptics as therapeutic compounds stabilizing neuromuscular transmission in amyotrophic lateral sclerosis

• DOI: 10.1172/jci.insight.97152
• Publication Date: 2017-11-15T16:00:38Z
• Authors: Shunmoogum A. Patten; Dina Aggad; Jose Martinez; Elsa Tremblay; Janet Petrillo; Gary A.B. Armstrong; Alexandre La Font...; Claudia Maios; Meijiang Liao; Sorana Ciura; Xiao-Yan Wen; Victor Rafuse; Justin Ichida; Lorne Zinman; Jean-Pierre Julien; Edor Kabashi; Richard Robitaille; Lawrence Korngut; J. Alexander Parker; Pierre Drapeau
• Keywords: Neuromuscular transmission; Pimozide

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, fatal disorder with no effective treatment. We used simple genetic models of ALS to screen phenotypically for potential therapeutic compounds. screened libraries compounds in C. elegans, validated hits zebrafish, and tested the most potent molecule mice small clinical trial. identified class neuroleptics that restored motility elegans was pimozide, which blocked T-type Ca2+ channels these stabilized neuromuscular transmission zebrafish enhanced it mice. Finally, short randomized controlled trial sporadic subjects demonstrated stabilization evidence target engagement at junction. Simple are, thus, useful identifying promising treatment ALS, such as neuroleptics, may stabilize prolong survival this disease.