{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T17:30:46Z","timestamp":1779298246057,"version":"3.51.4"},"reference-count":41,"publisher":"Portland Press Ltd.","issue":"3","license":[{"start":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T00:00:00Z","timestamp":1593388800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,6,30]]},"abstract":"<jats:p>Genetic approaches for the diagnosis and treatment of inherited muscle diseases have advanced rapidly in recent years. Many of the advances have occurred in the treatment of Duchenne muscular dystrophy (DMD), a muscle wasting disease where affected boys are typically wheelchair bound by age 12 years and generally die in their twenties from respiratory failure or cardiomyopathy. Dystrophin is a 421\u2005kD protein which links F-actin to the extracellular matrix via the dystrophin-associated protein complex (DAPC) at the muscle membrane. In the absence of dystrophin, the DAPC is lost, making the muscle membrane more susceptible to contraction-induced injury. The identification of the gene causing DMD in 1986 resulted in improved diagnosis of the disease and the identification of hotspots for mutation. There is currently no effective treatment. However, there are several promising genetic therapeutic approaches at the preclinical stage or in clinical trials including read-through of stop codons, exon skipping, delivery of dystrophin minigenes and the modulation of expression of the dystrophin related protein, utrophin. In spite of significant progress, the problem of targeting all muscles, including diaphragm and heart at sufficiently high levels, remains a challenge. Any therapy also needs to consider the immune response and some treatments are mutation specific and therefore limited to a subgroup of patients. This short review provides a summary of the current status of DMD therapy with a particular focus on those genetic strategies that have been taken to the clinic.<\/jats:p>","DOI":"10.1042\/bst20190282","type":"journal-article","created":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T12:00:31Z","timestamp":1593432031000},"page":"813-821","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["From diagnosis to therapy in Duchenne muscular dystrophy"],"prefix":"10.1042","volume":"48","author":[{"given":"Arran","family":"Babbs","sequence":"first","affiliation":[{"name":"MDUK Oxford Neuromuscular Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Chatzopoulou","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford OX 3TA, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ben","family":"Edwards","sequence":"additional","affiliation":[{"name":"MDUK Oxford Neuromuscular Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah E.","family":"Squire","sequence":"additional","affiliation":[{"name":"MDUK Oxford Neuromuscular Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel V.L.","family":"Wilkinson","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford OX 3TA, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham M.","family":"Wynne","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford OX 3TA, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela J.","family":"Russell","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Oxford OX 3TA, U.K."},{"name":"Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3PQ, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8807-8520","authenticated-orcid":false,"given":"Kay E.","family":"Davies","sequence":"additional","affiliation":[{"name":"MDUK Oxford Neuromuscular Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2020,6,29]]},"reference":[{"key":"2021111916020958900_BST-2019-0282CC1","doi-asserted-by":"publisher","first-page":"8a","DOI":"10.1085\/jgp.132.1.3a","article-title":"Maintenance of muscle cell membrane integrity and the pathogenesis of muscular dystrophy","volume":"132","year":"2008","journal-title":"J. Gen. Physiol."},{"key":"2021111916020958900_BST-2019-0282CC2","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1146\/annurev-genom-090314-025003","article-title":"The pathogenesis and therapy of muscular dystrophies","volume":"16","year":"2015","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"2021111916020958900_BST-2019-0282CC3","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1152\/physrev.00028.2001","article-title":"Function and genetics of dystrophin and dystrophin-related proteins in muscle","volume":"82","year":"2002","journal-title":"Physiol. Rev."},{"key":"2021111916020958900_BST-2019-0282CC4","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1016\/0092-8674(87)90579-4","article-title":"Dystrophin: the protein product of the Duchenne muscular dystrophy locus","volume":"51","year":"1987","journal-title":"Cell"},{"key":"2021111916020958900_BST-2019-0282CC5","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1002\/humu.22758","article-title":"The TREAT-NMD DMD global database: analysis of more than 7,000 Duchenne muscular dystrophy mutations","volume":"36","year":"2015","journal-title":"Hum. Mutat."},{"key":"2021111916020958900_BST-2019-0282CC6","doi-asserted-by":"publisher","first-page":"16","DOI":"10.3390\/jpm9010016","article-title":"Mutation-based therapeutic strategies for Duchenne muscular dystrophy: from genetic diagnosis to therapy","volume":"9","year":"2019","journal-title":"J. Pers. Med."},{"key":"2021111916020958900_BST-2019-0282CC7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/jpm9010001","article-title":"Restoring dystrophin expression in Duchenne muscular dystrophy: current status of therapeutic approaches","volume":"9","year":"2019","journal-title":"J. Pers. Med."},{"key":"2021111916020958900_BST-2019-0282CC8","doi-asserted-by":"publisher","first-page":"e15286","DOI":"10.1371\/journal.pone.0015286","article-title":"Marginal level dystrophin expression improves clinical outcome in a strain of dystrophin\/utrophin double knockout mice","volume":"5","year":"2010","journal-title":"PLoS ONE"},{"key":"2021111916020958900_BST-2019-0282CC9","doi-asserted-by":"publisher","first-page":"4225","DOI":"10.1093\/hmg\/ddv155","article-title":"How much dystrophin is enough: the physiological consequences of different levels of dystrophin in the mdx mouse","volume":"24","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"2021111916020958900_BST-2019-0282CC10","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.coph.2017.04.002","article-title":"Pharmacological advances for treatment in Duchenne muscular dystrophy","volume":"34","year":"2017","journal-title":"Curr. Opin. Pharmacol."},{"key":"2021111916020958900_BST-2019-0282CC11","doi-asserted-by":"publisher","first-page":"1458","DOI":"10.1113\/EP085308","article-title":"Advances in genetic therapeutic strategies for Duchenne muscular dystrophy","volume":"100","year":"2015","journal-title":"Exp. Physiol."},{"key":"2021111916020958900_BST-2019-0282CC12","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1089\/nat.2017.0682","article-title":"Development of exon skipping therapies for Duchenne muscular dystrophy: a critical review and a perspective on the outstanding issues","volume":"27","year":"2017","journal-title":"Nucleic Acid Ther."},{"key":"2021111916020958900_BST-2019-0282CC13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1089\/nat.2018.0747","article-title":"Cell-penetrating peptide conjugates of steric blocking oligonucleotides as therapeutics for neuromuscular diseases from a historical perspective to current prospects of treatment","volume":"29","year":"2019","journal-title":"Nucleic Acid Ther."},{"key":"2021111916020958900_BST-2019-0282CC14","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1038\/343180a0","article-title":"Very mild muscular-dystrophy associated with the deletion of 46-Percent of dystrophin","volume":"343","year":"1990","journal-title":"Nature"},{"key":"2021111916020958900_BST-2019-0282CC15","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1016\/j.ymthe.2017.02.019","article-title":"Progress toward gene therapy for Duchenne muscular dystrophy","volume":"25","year":"2017","journal-title":"Mol. Ther."},{"key":"2021111916020958900_BST-2019-0282CC16","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1016\/j.ymthe.2019.01.019","article-title":"Micro-dystrophin genes bring hope of an effective therapy for Duchenne muscular dystrophy","volume":"27","year":"2019","journal-title":"Mol. Ther."},{"key":"2021111916020958900_BST-2019-0282CC17","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1016\/j.ymthe.2019.01.002","article-title":"Development of novel micro-dystrophins with enhanced functionality","volume":"27","year":"2019","journal-title":"Mol. Ther."},{"key":"2021111916020958900_BST-2019-0282CC18","doi-asserted-by":"publisher","first-page":"2337","DOI":"10.1016\/j.ymthe.2018.07.011","article-title":"Systemic AAV micro-dystrophin gene therapy for duchenne muscular dystrophy","volume":"26","year":"2018","journal-title":"Mol. Ther."},{"key":"2021111916020958900_BST-2019-0282CC19","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms16105","article-title":"Long-term microdystrophin gene therapy is effective in a canine model of Duchenne muscular dystrophy","volume":"8","year":"2017","journal-title":"Nat. Commun."},{"key":"2021111916020958900_BST-2019-0282CC20","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1016\/j.nmd.2019.08.009","article-title":"Membrane recruitment of nNOS mu, in microdystrophin gene transfer to enhance durability","volume":"29","year":"2019","journal-title":"Neuromuscular Disord."},{"key":"2021111916020958900_BST-2019-0282CC21","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1038\/s41591-019-0594-0","article-title":"Non-immunogenic utrophin gene therapy for the treatment of muscular dystrophy animal models","volume":"25","year":"2019","journal-title":"Nat. Med."},{"key":"2021111916020958900_BST-2019-0282CC22","doi-asserted-by":"publisher","first-page":"38","DOI":"10.3390\/jpm8040038","article-title":"Applications of CRISPR\/Cas9 for the treatment of Duchenne muscular dystrophy","volume":"8","year":"2018","journal-title":"J. Pers. Med."},{"key":"2021111916020958900_BST-2019-0282CC23","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1146\/annurev-med-081117-010451","article-title":"CRISPR correction of Duchenne muscular dystrophy","volume":"70","year":"2019","journal-title":"Annu. Rev. Med."},{"key":"2021111916020958900_BST-2019-0282CC24","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1038\/s41591-019-0344-3","article-title":"Long-term evaluation of AAV-CRISPR genome editing for Duchenne muscular dystrophy","volume":"25","year":"2019","journal-title":"Nat. Med."},{"key":"2021111916020958900_BST-2019-0282CC25","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1093\/hmg\/ddy353","article-title":"Embryonic myosin is a regeneration marker to monitor utrophin-based therapies for DMD","volume":"28","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"2021111916020958900_BST-2019-0282CC26","doi-asserted-by":"publisher","first-page":"5723","DOI":"10.1073\/pnas.1323842111","article-title":"Microtubule binding distinguishes dystrophin from utrophin","volume":"111","year":"2014","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2021111916020958900_BST-2019-0282CC27","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1039\/9781782624202-00257","article-title":"Drug discovery approaches for rare neuromuscular diseases","volume":"2014","year":"2014","journal-title":"RSC Drug Discov. Series"},{"key":"2021111916020958900_BST-2019-0282CC28","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1080\/21678707.2018.1438261","article-title":"The potential of utrophin modulators for the treatment of Duchenne muscular dystrophy","volume":"6","year":"2018","journal-title":"Expert Opin. Orphan Drugs"},{"key":"2021111916020958900_BST-2019-0282CC29","doi-asserted-by":"publisher","first-page":"2547","DOI":"10.1021\/acs.jmedchem.9b01547","article-title":"Isolation, structural identification, synthesis, and pharmacological profiling of 1,2-trans-dihydro-1,2-diol metabolites of the utrophin modulator ezutromid","volume":"63","year":"2020","journal-title":"J. Med. Chem."},{"key":"2021111916020958900_BST-2019-0282CC30","doi-asserted-by":"publisher","first-page":"2420","DOI":"10.1002\/anie.201912392","article-title":"Chemical proteomics and phenotypic profiling identifies the aryl hydrocarbon receptor as a molecular target of the utrophin modulator ezutromid","volume":"59","year":"2020","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"2021111916020958900_BST-2019-0282CC31","doi-asserted-by":"publisher","first-page":"e0152840","DOI":"10.1371\/journal.pone.0152840","article-title":"Safety, tolerability, and pharmacokinetics of SMT C1100, a 2-arylbenzoxazole utrophin modulator, following single-and multiple-dose administration to pediatric patients with Duchenne muscular dystrophy","volume":"11","year":"2016","journal-title":"PLoS ONE"},{"key":"2021111916020958900_BST-2019-0282CC32","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1002\/jcph.468","article-title":"Safety, tolerability, and pharmacokinetics of SMT C1100, a 2-arylbenzoxazole utrophin modulator, following single-and multiple-dose administration to healthy male adult volunteers","volume":"55","year":"2015","journal-title":"J. Clin. Pharmacol."},{"key":"2021111916020958900_BST-2019-0282CC33","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1002\/cpdd.642","article-title":"A phase 1b trial to assess the pharmacokinetics of ezutromid in pediatric Duchenne muscular dystrophy patients on a balanced diet","volume":"8","year":"2019","journal-title":"Clin. Pharm. Drug Dev."},{"key":"2021111916020958900_BST-2019-0282CC34","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1038\/labinvest.2009.24","article-title":"Ah receptor represses acute-phase response gene expression without binding to its cognate response element","volume":"89","year":"2009","journal-title":"Lab Invest."},{"key":"2021111916020958900_BST-2019-0282CC35","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1124\/jpet.110.178392","article-title":"Identification of a high-Affinity ligand that exhibits complete aryl hydrocarbon receptor antagonism","volume":"338","year":"2011","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2021111916020958900_BST-2019-0282CC36","doi-asserted-by":"publisher","first-page":"38801","DOI":"10.1074\/jbc.M110.131573","article-title":"Identification of the aryl hydrocarbon receptor target gene TiPARP as a mediator of suppression of hepatic gluconeogenesis by 2,3,7,8-tetrachlorodibenzo-p-dioxin and of nicotinamide as a corrective agent for this effect","volume":"285","year":"2010","journal-title":"J Biol Chem."},{"key":"2021111916020958900_BST-2019-0282CC37","doi-asserted-by":"publisher","first-page":"C908","DOI":"10.1152\/ajpcell.00196.2005","article-title":"Calcineurin-NFAT signaling, together with GABP and peroxisome PGC-1 alpha, drives utrophin gene expression at the neuromuscular junction","volume":"289","year":"2005","journal-title":"Am. J. Physiol."},{"key":"2021111916020958900_BST-2019-0282CC38","doi-asserted-by":"publisher","first-page":"45","DOI":"10.3389\/fcell.2016.00045","article-title":"New trends in aryl hydrocarbon receptor biology","volume":"4","year":"2016","journal-title":"Front. Cell Dev. Biol."},{"key":"2021111916020958900_BST-2019-0282CC39","doi-asserted-by":"publisher","first-page":"551","DOI":"10.3389\/fimmu.2014.00551","article-title":"Aryl hydrocarbon receptor and kynurenine: recent advances in autoimmune disease research","volume":"5","year":"2014","journal-title":"Front. Immunol."},{"key":"2021111916020958900_BST-2019-0282CC40","doi-asserted-by":"publisher","first-page":"Abstract nr 1288","DOI":"10.1158\/1538-7445.AM2019-1288","article-title":"Blocking tumor-associated immune suppression with BAY-218, a novel, selective aryl hydrocarbon receptor (AhR) inhibitor","volume":"79","year":"2019","journal-title":"Cancer Res."},{"key":"2021111916020958900_BST-2019-0282CC41","doi-asserted-by":"publisher","first-page":"2189","DOI":"10.1093\/hmg\/ddz049","article-title":"The potential of utrophin and dystrophin combination therapies for Duchenne muscular dystrophy","volume":"28","year":"2019","journal-title":"Hum. Mol. Genet."}],"container-title":["Biochemical Society Transactions"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article-pdf\/48\/3\/813\/887015\/bst-2019-0282c.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article-pdf\/48\/3\/813\/887015\/bst-2019-0282c.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T16:23:56Z","timestamp":1637339036000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article\/48\/3\/813\/225554\/From-diagnosis-to-therapy-in-Duchenne-muscular"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,29]]},"references-count":41,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,6,29]]},"published-print":{"date-parts":[[2020,6,30]]}},"URL":"https:\/\/doi.org\/10.1042\/bst20190282","relation":{},"ISSN":["0300-5127","1470-8752"],"issn-type":[{"value":"0300-5127","type":"print"},{"value":"1470-8752","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,29]]}}}