{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T05:59:05Z","timestamp":1792735145295,"version":"4.5.0"},"reference-count":71,"publisher":"SAGE Publications","issue":"17-18","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:p>\n                    Facioscapulohumeral muscular dystrophy (FSHD) is a rare muscle dystrophy causing muscle weakness initially in the face, shoulders, and upper arms, and extends to lower body muscles as the disease progresses. Respiratory restriction in FSHD is increasingly reported to be more common and severe than previously thought, with the involvement of diaphragm weakness in pulmonary insufficiency being under debate. As aberrant expression of the double homeobox 4 (\n                    <jats:italic toggle=\"yes\">DUX4<\/jats:italic>\n                    ) gene is the prime cause of FSHD, we and others have developed numerous strategies and reported promising results on downregulating\n                    <jats:italic toggle=\"yes\">DUX4<\/jats:italic>\n                    expression in both cellular and animal models of FSHD. However, the effect of DUX4 and anti-DUX4 approaches on diaphragm muscle has not been elucidated. In this study, we show that toxic\n                    <jats:italic toggle=\"yes\">DUX4<\/jats:italic>\n                    expression causes pathology that affects the diaphragm of ACTA1-MCM\/FLExDUX4 mouse model of FSHD at both molecular and histological levels. Of importance, a systemic antisense treatment that suppresses\n                    <jats:italic toggle=\"yes\">DUX4<\/jats:italic>\n                    and target genes expression by 50% significantly improves muscle regeneration and muscle fibrosis, and prevents modification in myofiber type composition, supporting its development as a treatment for FSHD.\n                  <\/jats:p>","DOI":"10.1089\/hum.2021.251","type":"journal-article","created":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T23:13:18Z","timestamp":1643152398000},"page":"923-935","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":13,"title":["Improving Molecular and Histopathology in Diaphragm Muscle of the Double Transgenic ACTA1-MCM\/FLExDUX4 Mouse Model of FSHD with Systemic Antisense Therapy"],"prefix":"10.1177","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7241-9607","authenticated-orcid":false,"given":"Ngoc","family":"Lu-Nguyen","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Centre for Biomedical Sciences, School of Life Sciences and the Environment, Royal Holloway University of London, Egham, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0536-5231","authenticated-orcid":false,"given":"Alberto","family":"Malerba","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Centre for Biomedical Sciences, School of Life Sciences and the Environment, Royal Holloway University of London, Egham, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Antoni Pineda","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Centre for Biomedical Sciences, School of Life Sciences and the Environment, Royal Holloway University of London, Egham, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Dickson","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Centre for Biomedical Sciences, School of Life Sciences and the Environment, Royal Holloway University of London, Egham, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Popplewell","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Centre for Biomedical Sciences, School of Life Sciences and the Environment, Royal Holloway University of London, Egham, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2009.01158.x"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000797"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-016-0667-0"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncl.2014.04.003"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-018-00675-3"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.26717"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.24218"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000133126.86377.E8"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2017.03.008"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.21261"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2018.04.013"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2013.01.005"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.14142"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2016.08.014"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-016-8132-1"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-017-8525-9"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2009.05.014"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11325-019-01843-1"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1080\/09638288.2016.1212109"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000008123"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2015.04.011"},{"key":"e_1_3_5_23_2","first-page":"37","article-title":"Facioscapulohumeral muscular dystrophy and respiratory failure; What about the diaphragm?","volume":"14","author":"Hazenberg A","year":"2015","unstructured":"Hazenberg A, , van Alfen N, , Voet NBM, et al. 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