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While no precise biochemical mechanism or therapies are known, the pathogenesis of <jats:italic>CLN3<\/jats:italic> disease involves intracellular calcium accumulation that may trigger apoptosis. Our prior work in in vitro cell models of <jats:italic>CLN3<\/jats:italic> deficiency suggested that FDA\u2010approved calcium channel antagonists may have therapeutic value. To further evaluate the potential efficacy of this approach in an otherwise untreatable disorder, we sought to compare the therapeutic effects and underlying mechanisms in an animal model of <jats:italic>CLN3<\/jats:italic> disease. Here, we used the well\u2010characterized XT7 complete <jats:italic>cln\u20103<\/jats:italic> knockout strain of <jats:italic>C. elegans<\/jats:italic> to evaluate the therapeutic efficacy of calcium channel antagonist therapy in a living animal model of Batten disease. Therapeutic effects of five calcium channel antagonists were evaluated on XT7 animal lifespan and in vivo mitochondrial physiology. Remarkably, maximal therapeutic efficacy in this model animal was observed with 1 \u03bcM flunarizine, the identical concentration previously identified in cell\u2010based neuronal models of <jats:italic>CLN3<\/jats:italic> disease. Specifically, flunarizine rescued the short lifespan of XT7 worms and prevented their pathophysiologic mitochondrial accumulation. These results confirm the treatment efficacy and dosing of flunarizine in <jats:italic>cln\u20103<\/jats:italic> disease in a translational model organism. Clinical treatment trials in <jats:italic>CLN3<\/jats:italic> human patients are now needed to test the dosing regimen and efficacy of flunarizine in individuals suffering with this otherwise untreatable and ultimately lethal neurologic disease.<\/jats:p>","DOI":"10.1007\/s10545-016-9986-1","type":"journal-article","created":{"date-parts":[[2016,10,20]],"date-time":"2016-10-20T07:29:05Z","timestamp":1476948545000},"page":"291-296","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Flunarizine rescues reduced lifespan in <i>CLN3<\/i> triple knock\u2010out <i>Caenorhabditis elegans<\/i> model of batten disease"],"prefix":"10.1002","volume":"40","author":[{"given":"Young Joon","family":"Kwon","sequence":"first","affiliation":[{"name":"Division of Human Genetics, Department of Pediatrics The Children's Hospital of Philadelphia ARC 1002C, 3615 Civic Center Boulevard Philadelphia PA 19104 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