{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:19:00Z","timestamp":1791616740037,"version":"4.3.4"},"reference-count":48,"publisher":"American Society for Clinical Investigation","issue":"22","funder":[{"name":"several","award":["(see comments)"],"award-info":[{"award-number":["(see comments)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,11,16]]},"abstract":"<jats:p>\n                    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. We screened libraries of compounds in\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>elegans<\/jats:italic>\n                    , validated hits in zebrafish, and tested the most potent molecule in mice and in a small clinical trial. We identified a class of neuroleptics that restored motility in\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>elegans<\/jats:italic>\n                    and in zebrafish, and the most potent was pimozide, which blocked T-type Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channels in these simple models and stabilized neuromuscular transmission in zebrafish and enhanced it in mice. Finally, a short randomized controlled trial of sporadic ALS subjects demonstrated stabilization of motility and evidence of target engagement at the neuromuscular junction. Simple genetic models are, thus, useful in identifying promising compounds for the treatment of ALS, such as neuroleptics, which may stabilize neuromuscular transmission and prolong survival in this disease.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.97152","type":"journal-article","created":{"date-parts":[[2017,11,15]],"date-time":"2017-11-15T11:00:38Z","timestamp":1510743638000},"source":"Crossref","is-referenced-by-count":114,"title":["Neuroleptics as therapeutic compounds stabilizing neuromuscular transmission in amyotrophic lateral sclerosis"],"prefix":"10.1172","volume":"2","author":[{"given":"Shunmoogum A.","family":"Patten","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Canada."},{"name":"Centre de recherche du centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al (CRCHUM), Montr\u00e9al, Canada."},{"name":"INRS Institut Armand-Frappier, Laval, 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