{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:32:56Z","timestamp":1791973976951,"version":"4.4.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"19","license":[{"start":{"date-parts":[[2019,7,2]],"date-time":"2019-07-02T00:00:00Z","timestamp":1562025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100007393","name":"French Association against Myopathies","doi-asserted-by":"publisher","award":["17110"],"award-info":[{"award-number":["17110"]}],"id":[{"id":"10.13039\/100007393","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007393","name":"French Association against Myopathies","doi-asserted-by":"publisher","award":["15123"],"award-info":[{"award-number":["15123"]}],"id":[{"id":"10.13039\/100007393","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012946","name":"Sorbonne University association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012946","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Institute of Myology"},{"DOI":"10.13039\/501100001677","name":"National Institute of Health and Medical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Oculopharyngeal muscular dystrophy (OPMD) is a rare autosomal dominant late-onset muscular dystrophy affecting approximately 1:100\u2009000 individuals in Europe. OPMD is mainly characterized by progressive eyelid drooping (ptosis) and dysphagia although muscles of the limbs can also be affected late in life. This muscle disease is due to a trinucleotide repeat expansion in the polyA-binding protein nuclear-1 gene. Patients express a protein with an 11\u201318 alanine tract that is misfolded and prone to form intranuclear inclusions, which are the hallmark of the disease. Other features of OPMD include muscle fibrosis and atrophy in affected muscles. Currently, no pharmacological treatments are available, and OPMD patients can only be referred to surgeons for cricopharyngeal myotomy or corrective surgery of extraocular muscles to ease ptosis. We recently tested a two-AAV `silence\u2019 and `replace\u2019 vector-based gene therapy treatment in a mouse model of OPMD. We demonstrate here that this gene therapy approach can revert already established insoluble aggregates and partially rescues the muscle from atrophy, which are both crucially important since in most cases OPMD patients already have an established disease when diagnosed. This strategy also prevents the formation of muscle fibrosis and stabilizes the muscle strength to the level of healthy muscles. Furthermore, we show here that similar results can be obtained using a single AAV vector incorporating both the `silence\u2019 and `replace\u2019 cassettes. These results further support the application of a gene therapy approach as a novel treatment for OPMD in humans.<\/jats:p>","DOI":"10.1093\/hmg\/ddz167","type":"journal-article","created":{"date-parts":[[2019,7,8]],"date-time":"2019-07-08T15:09:51Z","timestamp":1562598591000},"page":"3301-3308","source":"Crossref","is-referenced-by-count":11,"title":["Established PABPN1 intranuclear inclusions in OPMD muscle can be efficiently reversed by AAV-mediated knockdown and replacement of mutant expanded PABPN1"],"prefix":"10.1093","volume":"28","author":[{"given":"Alberto","family":"Malerba","sequence":"first","affiliation":[{"name":"Centres of Gene and Cell Therapy and Biomedical Sciences, School of Biological Sciences, Royal Holloway, University of London, Egham TW20 0EX, Surrey, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Klein","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, Association Institut de Myologie, Centre de Recherche en Myologie, UMRS974, 47 bd de l\u2019H\u00f4pital, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"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 TW20 0EX, Surrey, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ornella","family":"Cappellari","sequence":"first","affiliation":[{"name":"Comparative Biomedical Sciences, Royal Veterinary College, London NW1 0TU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Strings-Ufombah","sequence":"first","affiliation":[{"name":"Benitec Biopharma, Hayward, CA 94545, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonal","family":"Harbaran","sequence":"first","affiliation":[{"name":"Benitec Biopharma, Hayward, CA 94545, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Roelvink","sequence":"first","affiliation":[{"name":"Benitec Biopharma, Hayward, CA 94545, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Suhy","sequence":"first","affiliation":[{"name":"Benitec Biopharma, Hayward, CA 94545, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Capucine","family":"Trollet","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, Association Institut de Myologie, Centre de Recherche en Myologie, UMRS974, 47 bd de l\u2019H\u00f4pital, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Dickson","sequence":"first","affiliation":[{"name":"Centres of Gene and Cell Therapy and Biomedical Sciences, School of Biological Sciences, Royal Holloway, University of London, Egham TW20 0EX, Surrey, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,7,2]]},"reference":[{"key":"2020070812441467300_ref1","doi-asserted-by":"crossref","first-page":"2437","DOI":"10.1001\/jama.286.19.2437","article-title":"Oculopharyngeal muscular dystrophy in Hispanic New Mexicans","volume":"286","author":"Becher","year":"2001","journal-title":"JAMA"},{"key":"2020070812441467300_ref2","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.jfma.2011.06.017","article-title":"Oculopharyngeal muscular dystrophy\u2014an under-diagnosed disease in China? Report a China-born Chinese with PABPN1 mutation and epidemiology review of the literature","volume":"111","author":"Chien","year":"2012","journal-title":"J. Formos. Med. Assoc."},{"key":"2020070812441467300_ref3","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1136\/jim-2016-000184","article-title":"Characterization of PABPN1 expansion mutations in a large cohort of Mexican patients with oculopharyngeal muscular dystrophy (OPMD)","volume":"65","author":"Cruz-Aguilar","year":"2017","journal-title":"J. Investig. 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