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S48168\/ARM210, an RyR calcium release channel stabilizer (a Rycal compound), is expected to enhance the rebinding of calstabin to the RyR channel complex and possibly alleviate the pathologic Ca\n                    <jats:sup>2+<\/jats:sup>\n                    leakage in dystrophin\u2010deficient skeletal and cardiac muscle. This study systematically investigated the effect of S48168\/ARM210 on the phenotype of\n                    <jats:italic>mdx<\/jats:italic>\n                    mice by means of a first proof\u2010of\u2010concept, short (4 wk), phase 1 treatment, followed by a 12\u2010wk treatment (phase 2) performed in parallel by 2 independent laboratories. The\n                    <jats:italic>mdx<\/jats:italic>\n                    mice were treated with S48168\/ARM210 at two different concentrations (50 or 10 mg\/kg\/d) in their drinking water for 4 and 12 wk, respectively. The mice were subjected to treadmill sessions twice per week (12 m\/min for 30 min) to unmask the mild disease. This testing was followed by\n                    <jats:italic>in vivo<\/jats:italic>\n                    forelimb and hindlimb grip strength and fatigability measurement,\n                    <jats:italic>ex vivo<\/jats:italic>\n                    extensor digitorum longus (EDL) and diaphragm (DIA) force contraction measurement and histologic and biochemical analysis. The treatments resulted in functional (grip strength, ex vivo force production in DIA and EDL muscles) as well as histologic improvement after 4 and 12 wk, with no adverse effects. Furthermore, levels of cellular biomarkers of calcium homeostasis increased. Therefore, these data suggest that S48168\/ARM210 may be a safe therapeutic option, at the dose levels tested, for the treatment of Duchenne muscular dystrophy (DMD).\u2014Capogrosso, R. F., Mantuano, P., Uaesoontrachoon, K., Cozzoli, A., Giustino, A., Dow, T., Srinivassane, S., Filipovic, M., Bell, C., Vandermeulen, J., Massari, A. M., De Bellis, M., Conte, E., Pierno, S., Camerino, G. M., Liantonio, A., Nagaraju, K., De Luca, A. Ryanodine channel complex stabilizer compound S48168\/ARM210 as a disease modifier in dystrophin\u2010deficient mdx mice: proof\u2010of\u2010concept study and independent validation of efficacy.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    32, 1025\u20131043 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201700182rrr","type":"journal-article","created":{"date-parts":[[2017,11,2]],"date-time":"2017-11-02T12:25:40Z","timestamp":1509625540000},"page":"1025-1043","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Ryanodine channel complex stabilizer compound S48168\/ARM210 as a disease modifier in dystrophin\u2010deficient\n                    <i>mdx<\/i>\n                    mice: proof\u2010of\u2010concept study and independent validation of efficacy"],"prefix":"10.1096","volume":"32","author":[{"given":"Roberta Francesca","family":"Capogrosso","sequence":"first","affiliation":[{"name":"Pharmacology Unit Department of Pharmacy\u2013Drug Sciences University of Bari Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Mantuano","sequence":"additional","affiliation":[{"name":"Pharmacology Unit Department of Pharmacy\u2013Drug Sciences University of Bari Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kitipong","family":"Uaesoontrachoon","sequence":"additional","affiliation":[{"name":"Agada Biosciences, Incorporated Halifax Nova Scotia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Cozzoli","sequence":"additional","affiliation":[{"name":"Pharmacology Unit Department of Pharmacy\u2013Drug Sciences University of Bari Bari 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