{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T21:10:30Z","timestamp":1790025030243,"version":"4.0.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2019,6,10]],"date-time":"2019-06-10T00:00:00Z","timestamp":1560124800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100011724","name":"Muscular Dystrophy UK","doi-asserted-by":"publisher","award":["RA\/893"],"award-info":[{"award-number":["RA\/893"]}],"id":[{"id":"10.13039\/100011724","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Duchenne muscular dystrophy (DMD) is a rare genetic disease affecting 1 in 3500\u20135000 newborn boys. It is due to mutations in the DMD gene with a consequent lack of dystrophin protein that leads to deterioration of myofibres and their replacement with fibro-adipogenic tissue. Out-of-frame mutations in the DMD gene can be modified by using antisense oligonucleotides (AONs) to promote skipping of specific exons such that the reading frame is restored and the resulting protein produced, though truncated, is functional. We have shown that AONs can also be used to knock down myostatin, a negative regulator of muscle growth and differentiation, through disruption of the transcript reading frame, and thereby enhance muscle strength. In young mdx mice, combined dystrophin and myostatin exon skipping therapy greatly improved DMD pathology, compared to the single dystrophin skipping approach. Here we show that in aged (&gt;15-month-old) mdx mice, when the pathology is significantly more severe and more similar to the one observed in DMD patients, the effect of the combined therapy is slightly attenuated but still beneficial in improving the disease phenotype. These results confirm the beneficial outcome of the combination approach and support its translation into DMD clinical trials.<\/jats:p>","DOI":"10.1093\/hmg\/ddz125","type":"journal-article","created":{"date-parts":[[2019,6,7]],"date-time":"2019-06-07T11:08:31Z","timestamp":1559905711000},"source":"Crossref","is-referenced-by-count":7,"title":["Functional muscle recovery following dystrophin and myostatin exon splice modulation in aged mdx mice"],"prefix":"10.1093","author":[{"given":"Ngoc","family":"Lu-Nguyen","sequence":"first","affiliation":[{"name":"Centres of Gene and Cell Therapy and Biomedical Sciences, School of Biological Sciences, Royal Holloway-University of London, Egham, Surrey, TW20 0EX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Ferry","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9 UMRS974 INSERM, Institut de Myologie, 75013 Paris, France"},{"name":"Universit\u00e9 Sorbonne Paris Cit\u00e9, 75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick J","family":"Schnell","sequence":"additional","affiliation":[{"name":"Sarepta Therapeutics, Inc., 215 First Street, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar J","family":"Hanson","sequence":"additional","affiliation":[{"name":"Sarepta Therapeutics, Inc., 215 First Street, Cambridge, MA 02142, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Popplewell","sequence":"additional","affiliation":[{"name":"Centres of Gene and Cell Therapy and Biomedical Sciences, School of Biological Sciences, Royal Holloway-University of London, Egham, Surrey, TW20 0EX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Dickson","sequence":"additional","affiliation":[{"name":"Centres of Gene and Cell Therapy and Biomedical Sciences, School of Biological Sciences, Royal Holloway-University of London, Egham, Surrey, TW20 0EX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Malerba","sequence":"additional","affiliation":[{"name":"Centres of Gene and Cell Therapy and Biomedical Sciences, School of Biological Sciences, Royal Holloway-University of London, Egham, Surrey, TW20 0EX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,6,10]]},"reference":[{"key":"2019073002501697300_ref1","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1002\/mus.24880","article-title":"Twenty-year follow-up of newborn screening for patients with muscular dystrophy","volume":"53","author":"Chung","year":"2015","journal-title":"Muscle Nerve"},{"key":"2019073002501697300_ref2","doi-asserted-by":"crossref","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","author":"Hoffman","year":"1987","journal-title":"Cell"},{"key":"2019073002501697300_ref3","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1083\/jcb.112.1.135","article-title":"Dystrophin-glycoprotein complex is highly enriched in isolated skeletal muscle sarcolemma","volume":"112","author":"Ohlendieck","year":"1991","journal-title":"J. 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