{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:23:52Z","timestamp":1790767432643,"version":"4.1.0"},"reference-count":52,"publisher":"American Society for Clinical Investigation","issue":"7","license":[{"start":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T00:00:00Z","timestamp":1617840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,8]]},"abstract":"<jats:p>Gene replacement for Duchenne muscular dystrophy (DMD) with micro-dystrophins has entered clinical trials, but efficacy in preventing heart failure is unknown. Although most patients with DMD die from heart failure, cardiomyopathy is undetectable until the teens, so efficacy from trials in young boys will be unknown for a decade. Available DMD animal models were sufficient to demonstrate micro-dystrophin efficacy on earlier onset skeletal muscle pathology underlying loss of ambulation and respiratory insufficiency in patients. However, no mouse models progressed into heart failure, and dog models showed highly variable progression insufficient to evaluate efficacy of micro-dystrophin or other therapies on DMD heart failure. To overcome this barrier, we have generated the first DMD mouse model to our knowledge that reproducibly progresses into heart failure. This model shows cardiac inflammation and fibrosis occur prior to reduced function. Fibrosis does not continue to accumulate, but inflammation persists after function declines. We used this model to test micro-dystrophin gene therapy efficacy on heart failure prevention for the first time. Micro-dystrophin prevented declines in cardiac function and prohibited onset of inflammation and fibrosis. This model will allow identification of committed pathogenic steps to heart failure and testing of genetic and nongenetic therapies to optimize cardiac care for patients with DMD.<\/jats:p>","DOI":"10.1172\/jci.insight.146511","type":"journal-article","created":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T12:00:44Z","timestamp":1614686444000},"source":"Crossref","is-referenced-by-count":30,"title":["Micro-dystrophin gene therapy prevents heart failure in an improved Duchenne muscular dystrophy cardiomyopathy mouse model"],"prefix":"10.1172","volume":"6","author":[{"given":"Zachary M.","family":"Howard","sequence":"first","affiliation":[{"name":"Department of Physiology & Cell Biology and Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2883-8644","authenticated-orcid":true,"given":"Lisa E.","family":"Dorn","sequence":"additional","affiliation":[{"name":"Department of Physiology & Cell Biology and Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeovanna","family":"Lowe","sequence":"additional","affiliation":[{"name":"Department of Physiology & Cell Biology and Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan D.","family":"Gertzen","sequence":"additional","affiliation":[{"name":"Department of Physiology & Cell Biology and Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierce","family":"Ciccone","sequence":"additional","affiliation":[{"name":"Department of Physiology & Cell Biology and Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha","family":"Rastogi","sequence":"additional","affiliation":[{"name":"Department of Physiology & Cell Biology and Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy L.","family":"Odom","sequence":"additional","affiliation":[{"name":"Department of Neurology and Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center, University of Washington, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Accornero","sequence":"additional","affiliation":[{"name":"Department of Physiology & Cell Biology and Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5299-0059","authenticated-orcid":true,"given":"Jeffrey S.","family":"Chamberlain","sequence":"additional","affiliation":[{"name":"Department of Neurology and Senator Paul D. Wellstone Muscular Dystrophy Specialized Research Center, University of Washington, Seattle, Washington, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3239-8530","authenticated-orcid":true,"given":"Jill A.","family":"Rafael-Fortney","sequence":"additional","affiliation":[{"name":"Department of Physiology & Cell Biology and Davis Heart and Lung Research Institute, College of Medicine, The Ohio State University, Columbus, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2021,4,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-090314-025003"},{"issue":"8","key":"B2","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0043515","article-title":"Proteomic analysis reveals new cardiac-specific dystrophin-associated proteins","volume":"7","author":"Johnson","year":"2012","journal-title":"PLoS One"},{"issue":"17","key":"B3","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20174098","article-title":"Cardiac pathophysiology and the future of cardiac therapies in duchenne muscular dystrophy","volume":"20","author":"Meyers","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1096\/fj.10-178913"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.1484"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.015151"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/nm1085"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2019.01.002"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2008.264"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2011.03.010"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/nm1439"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300144"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2017.144"},{"key":"B14","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms16105","article-title":"Long-term microdystrophin gene therapy is effective in a canine model of Duchenne muscular dystrophy","volume":"8","author":"Le Guiner","year":"2017","journal-title":"Nat Commun"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2012.81"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2012.05.002"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-8966(02)00286-9"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00448.2005"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2004.11.025"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.110.960740"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-014-0972-9"},{"key":"B22","doi-asserted-by":"crossref","DOI":"10.1186\/1532-429X-15-107","article-title":"Prevalence and distribution of late gadolinium enhancement in a large population of patients with Duchenne muscular dystrophy: effect of age and left ventricular systolic function","volume":"15","author":"Hor","year":"2013","journal-title":"J Cardiovasc Magn Reson"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/ng0598-79"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80532-2"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/4033"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.031716"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70318-7"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000958"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/s10554-010-9781-2"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2012.05.002"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.2217\/bmm-2018-0125"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddz128"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1002\/mus.21763"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2017.06.006"},{"key":"B35","article-title":"Cardiac fibrosis","author":"Frangogiannis","journal-title":"Cardiovasc Res"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2008.04.005"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.carpath.2014.10.006"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.14018"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2006.02.003"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2008.52"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/345315a0"},{"issue":"5\u20136","key":"B42","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s10974-013-9362-9","article-title":"Alterations of dystrophin-associated glycoproteins in the heart lacking dystrophin or dystrophin and utrophin","volume":"34","author":"Sharpe","year":"2013","journal-title":"J Muscle Res Cell Motil"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1512991112"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1172\/JCI36612"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1999.1018"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2019.06.006"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3233\/JND-150099"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/ng1294-333"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.134.1.93"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3233\/JND-180323"},{"key":"B51","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2019.01324","article-title":"Mineralocorticoid receptor signaling contributes to normal muscle repair after acute injury","volume":"10","author":"Hauck","year":"2019","journal-title":"Front Physiol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7374-3_18"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/146511\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:44:45Z","timestamp":1779151485000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/146511"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,8]]},"references-count":52,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,4,8]]},"published-print":{"date-parts":[[2021,4,8]]}},"alternative-id":["10.1172\/jci.insight.146511"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.146511","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,8]]},"article-number":"e146511"}}