{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T17:41:26Z","timestamp":1775497286609,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR063182"],"award-info":[{"award-number":["AR063182"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["AR078198"],"award-info":[{"award-number":["AR078198"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2026,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n Introduction\/Aims<\/jats:title>\n \n Effective management remains lacking for recurrent episodes of acute weakness in hypokalemic periodic paralysis (HypoPP). We assessed the efficacy of a second\u2010generation potassium channel agonist, XEN1101, to prevent and abort the low\u2010K\n +<\/jats:sup>\n induced loss of force in mouse models of HypoPP.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n An ex\u00a0vivo contractility assay was used to interrogate the efficacy of XEN1101 for preserving contractile force and for enhancing recovery of force in the setting of a low\u2010K\n +<\/jats:sup>\n challenge for HypoPP mice carrying the sodium channel Na\n V<\/jats:sub>\n 1.4\u2010R669H or the calcium channel Ca\n V<\/jats:sub>\n 1.1\u2010R528H mutations.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The acute loss of force for HypoPP muscle, triggered by a 2\u2009mM\u2009K\n +<\/jats:sup>\n challenge, was prevented by low micromolar XEN1101, with an effective concentration of 0.30\u2009\u03bcM for 50% protection. Application of 1\u2009\u03bcM XEN1101, after the onset of 2\u2009mM\u2009K\n +<\/jats:sup>\n induced weakness, restored the peak contractile force (70%\u2013100% of baseline).\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n The K\n V<\/jats:sub>\n 7 potassium channel agonist XEN1101 is effective as both a prophylactic agent and as abortive therapy for management of low\u2010K\n +<\/jats:sup>\n induced weakness in murine models of HypoPP. XEN1101 is more potent than the first\u2010generation Kv7 agonist, retigabine, in our murine models of HypoPP and is also better tolerated in patients. These improvements provide a rationale for future clinical trials of XEN1101 in HypoPP patients.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mus.70159","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T11:17:14Z","timestamp":1768994234000},"page":"668-674","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy of a K\n +<\/sup>\n Channel Agonist,\n XEN1101<\/scp>\n , For Preserving Contractility in Mouse Models of Hypokalemic Periodic Paralysis"],"prefix":"10.1002","volume":"73","author":[{"given":"Viktor","family":"Chanchykov","sequence":"first","affiliation":[{"name":"Department of Physiology David Geffen School of Medicine at UCLA Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon","family":"Iype","sequence":"additional","affiliation":[{"name":"Department of Physiology David Geffen School of Medicine at UCLA Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marbella","family":"Quinonez","sequence":"additional","affiliation":[{"name":"Department of Physiology David Geffen School of Medicine at UCLA Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fenfen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Physiology David Geffen School of Medicine at UCLA Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8428-3690","authenticated-orcid":false,"given":"Stephen","family":"Cannon","sequence":"additional","affiliation":[{"name":"Department of Physiology David Geffen School of Medicine at UCLA Los Angeles California USA"},{"name":"Department of Neurology David Geffen School of Medicine at UCLA Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-323-90820-7.00002-1"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.26009"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11940-020-00644-2"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31823a0cb6"},{"key":"e_1_2_13_6_1","first-page":"e40","article-title":"Annual Renal Ultrasound May Prevent Acute Presentatino With Acetazolamide\u2010Associated Urolithiasis","volume":"11","author":"Suetterlin K.","year":"2019","journal-title":"Neurology Clinical Practice"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2024.05.012"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2015.tb00630.x"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI57398"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI66091"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.880130513"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0960-8966(94)00036-9"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2012.706278"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16725"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/803082"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2019.02.002"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac441"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2023.3542"},{"key":"e_1_2_13_19_1","first-page":"1437","article-title":"Targeted Mutation of Mouse Skeletal Muscle Sodium Channel Produces Myotonia and Potassium\u2010Sensitive Weakness","volume":"118","author":"Hayward L. J.","year":"2008","journal-title":"Journal of Clinical Investigation"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182886a0e"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2418021122"}],"container-title":["Muscle & Nerve"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.70159","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mus.70159","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.70159","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T16:14:58Z","timestamp":1775492098000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mus.70159"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,21]]},"references-count":20,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/mus.70159"],"URL":"https:\/\/doi.org\/10.1002\/mus.70159","archive":["Portico"],"relation":{},"ISSN":["0148-639X","1097-4598"],"issn-type":[{"value":"0148-639X","type":"print"},{"value":"1097-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,21]]},"assertion":[{"value":"2025-08-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}