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To study the pathophysiology of LEMS and test candidate therapeutic strategies, a passive\u2010transfer animal model has been developed in mice, which can be created by daily intraperitoneal injections of LEMS patient serum or IgG into mice for 2\u20134 weeks. Results from studies of the mouse neuromuscular junction have revealed that each synapse has hundreds of transmitter release sites but that the probability for release at each one is likely to be low. LEMS further reduces this low probability such that transmission is no longer effective at triggering a muscle contraction. The LEMS\u2010mediated attack reduces the number of presynaptic calcium channels, disorganizes transmitter release sites, and results in the homeostatic upregulation of other calcium channel types. Symptomatic treatment is focused on increasing the probability of release from dysfunctional release sites. Current treatment uses the potassium channel blocker 3,4\u2010diaminopyridine (DAP) to broaden the presynaptic action potential, providing more time for calcium channels to open. Current research is focused on testing new calcium channel gating modifiers that work synergistically with DAP.<\/jats:p>","DOI":"10.1111\/nyas.13512","type":"journal-article","created":{"date-parts":[[2017,11,10]],"date-time":"2017-11-10T12:48:39Z","timestamp":1510318119000},"page":"73-81","source":"Crossref","is-referenced-by-count":20,"title":["Lambert\u2013Eaton myasthenic syndrome: mouse passive\u2010transfer model illuminates disease pathology and facilitates testing therapeutic leads"],"prefix":"10.1111","volume":"1412","author":[{"given":"Stephen D.","family":"Meriney","sequence":"first","affiliation":[{"name":"Department of Neuroscience University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tyler B.","family":"Tarr","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristine S.","family":"Ojala","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Man","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yizhi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Lacomis","sequence":"additional","affiliation":[{"name":"Division of Neuromuscular Diseases, Departments of Neurology and Pathology University of Pittsburgh Medical Center Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adolfo","family":"Garcia\u2010Oca\u00f1a","sequence":"additional","affiliation":[{"name":"Diabetes, Obesity and Metabolism Institute Icahn School of Medicine at Mount Sinai New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillermo","family":"Valdomir","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Wipf","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,11,10]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"612","article-title":"Defect of neuromuscular conduction associated with malignant neoplasm","volume":"187","author":"Lambert E.H.","year":"1956","journal-title":"Am. 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