{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T13:49:13Z","timestamp":1785160153140,"version":"3.55.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T00:00:00Z","timestamp":1708041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Epidermolysis Bullosa Research Partnership"},{"DOI":"10.13039\/100002077","name":"Epidermolysis Bullosa Medical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002077","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Directed Medical Research Program"},{"name":"VA Merit Award"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Recessive dystrophic epidermolysis bullosa (RDEB) is an incurable widespread blistering skin disorder caused by mutations in the gene encoding for type VII collagen (C7), the major component of anchoring fibrils.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To evaluate the efficacy and safety of intravenous (IV) gentamicin readthrough therapy in patients with RDEB harbouring nonsense mutations. The primary outcomes were increased expression of C7 in patients\u2019 skin and safety assessments (ototoxicity, nephrotoxicity, autoimmune response); secondary outcomes included measuring wound healing in target wounds and assessment by a validated Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) scoring system.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>An open-label pilot trial to assess two different IV gentamicin regimens between August 2018 and March 2020 with follow-up through to 180\u2005days post-treatment was carried out. Three patients with RDEB with confirmed nonsense mutations in COL7A1 in either one or two alleles and decreased baseline expression of C7 at the dermal\u2013epidermal junction (DEJ) of their skin participated in the study. Three patients received gentamicin 7.5\u2005mg kg\u20131 daily for 14\u2005days and two of the three patients further received 7.5\u2005mg kg\u20131 IV gentamicin twice weekly for 12 weeks. Patients who had pre-existing auditory or renal impairment, were currently using ototoxic or nephrotoxic medications, or had allergies to aminoglycosides or sulfate compounds were excluded.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>After gentamicin treatment, skin biopsies from all three patients (age range 18\u201328\u2005years) exhibited increased C7 in their DEJ. With both regimens, the new C7 persisted for at least 6\u2005months post-treatment. At 1 and 3\u2005months post-treatment, 100% of the monitored wounds exhibited &amp;gt; 85% closure. Both IV gentamicin infusion regimens decreased EBDASI total activity scores. Of the patients assessed with the EBDASI, all exhibited decreased total activity scores 3\u2005months post-treatment. All three patients completed the study; no adverse effects or anti-C7 antibodies were detected.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>IV gentamicin induced the readthrough of nonsense mutations in patients with RDEB and restored functional C7 in their skin, enhanced wound healing and improved clinical parameters. IV gentamicin may be a safe, efficacious, low-cost and readily available treatment for this population of patients with RDEB.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bjd\/ljae063","type":"journal-article","created":{"date-parts":[[2024,2,17]],"date-time":"2024-02-17T07:35:43Z","timestamp":1708155343000},"page":"267-274","source":"Crossref","is-referenced-by-count":15,"title":["Intravenous gentamicin therapy induces functional type VII collagen in patients with recessive dystrophic epidermolysis bullosa: an open-label clinical trial"],"prefix":"10.1093","volume":"191","author":[{"given":"David T","family":"Woodley","sequence":"first","affiliation":[{"name":"Department of Dermatology, The Keck School of Medicine, University of Southern California , Los Angeles, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Keck School of Medicine, University of Southern California , Los Angeles, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Kwong","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Keck School of Medicine, University of Southern California , Los Angeles, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon","family":"Levian","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Keck School of Medicine, University of Southern California , Los Angeles, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Cogan","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Keck School of Medicine, University of Southern California , Los Angeles, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingping","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Keck School of Medicine, University of Southern California , Los Angeles, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Mosallaei","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Keck School of Medicine, University of Southern California , Los Angeles, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elana","family":"Kleinman","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Keck School of Medicine, University of Southern California , Los Angeles, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Keck School of Medicine, University of Southern California , Los Angeles, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Keck School of Medicine, University of Southern California , Los Angeles, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gene","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Keck School of Medicine, University of Southern California , Los Angeles, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Keck School of Medicine, University of Southern California , Los Angeles, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6809-147X","authenticated-orcid":false,"given":"Mei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The Keck School of Medicine, University of Southern California , Los Angeles, CA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,2,16]]},"reference":[{"key":"2024071611290067300_ljae063-B1","author":"Pfendner"},{"key":"2024071611290067300_ljae063-B2","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1172\/JCI115938","article-title":"Molecular genetics of the cutaneous basement membrane zone. Perspectives on epidermolysis bullosa and other blistering skin diseases","volume":"90","author":"Uitto","year":"1992","journal-title":"J Clin Invest"},{"key":"2024071611290067300_ljae063-B3","doi-asserted-by":"crossref","first-page":"6931","DOI":"10.1073\/pnas.88.16.6931","article-title":"Human type VII collagen: cDNA cloning and chromosomal mapping of the gene","volume":"88","author":"Parente","year":"1991","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2024071611290067300_ljae063-B4","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-211-79271-1","volume-title":"Life with Epidermolysis Bullosa (EB): Etiology, Diagnosis, Multidisciplinary Care and Therapy","author":"Fine","year":"2009"},{"key":"2024071611290067300_ljae063-B5","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1111\/pde.13276","article-title":"Inpatient management of children with recessive dystrophic epidermolysis bullosa: a review","volume":"34","author":"Li","year":"2017","journal-title":"Pediatr Dermatol"},{"key":"2024071611290067300_ljae063-B6","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1080\/2000656X.2019.1661846","article-title":"Surgical management of hand deformities in patients with recessive dystrophic epidermolysis bullosa","volume":"54","author":"Zhou","year":"2020","journal-title":"J Plast Surg Hand Surg"},{"key":"2024071611290067300_ljae063-B7","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/sj.mt.6300041","article-title":"Intravenously injected human fibroblasts home to skin wounds, deliver type VII collagen, and promote wound healing","volume":"15","author":"Woodley","year":"2007","journal-title":"Mol Ther J Am Soc Gene Ther"},{"key":"2024071611290067300_ljae063-B8","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/nm1063","article-title":"Injection of recombinant human type VII collagen restores collagen function in dystrophic epidermolysis bullosa","volume":"10","author":"Woodley","year":"2004","journal-title":"Nat Med"},{"key":"2024071611290067300_ljae063-B9","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/ng1041","article-title":"Restoration of type VII collagen expression and function in dystrophic epidermolysis bullosa","volume":"32","author":"Chen","year":"2002","journal-title":"Nat Genet"},{"key":"2024071611290067300_ljae063-B10","doi-asserted-by":"crossref","first-page":"455","DOI":"10.2147\/TCRM.S386923","article-title":"Innovations in the treatment of dystrophic epidermolysis bullosa (DEB): current landscape and prospects","volume":"19","author":"Hou","year":"2023","journal-title":"Ther Clin Risk Manag"},{"key":"2024071611290067300_ljae063-B11","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1056\/NEJMoa0910501","article-title":"Bone marrow transplantation for recessive dystrophic epidermolysis bullosa","volume":"363","author":"Wagner","year":"2010","journal-title":"N Engl J Med"},{"key":"2024071611290067300_ljae063-B12","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1001\/jama.2016.15588","article-title":"Safety and wound outcomes following genetically corrected autologous epidermal grafts in patients with recessive dystrophic epidermolysis bullosa","volume":"316","author":"Siprashvili","year":"2016","journal-title":"JAMA"},{"key":"2024071611290067300_ljae063-B13","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1056\/NEJMoa2206663","article-title":"Trial of Beremagene Geperpavec (B-VEC) for dystrophic epidermolysis bullosa","volume":"387","author":"Guide","year":"2022","journal-title":"N Engl J Med"},{"key":"2024071611290067300_ljae063-B14","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.tig.2008.08.010","article-title":"Introducing sense into nonsense in treatments of human genetic diseases","volume":"24","author":"Linde","year":"2008","journal-title":"Trends Genet"},{"key":"2024071611290067300_ljae063-B15","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.molmed.2012.09.008","article-title":"Sense from nonsense: therapies for premature stop codon diseases","volume":"18","author":"Bidou","year":"2012","journal-title":"Trends Mol Med"},{"key":"2024071611290067300_ljae063-B16","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1172\/JCI7866","article-title":"Aminoglycoside antibiotics restore dystrophin function to skeletal muscles of mdx mice","volume":"104","author":"Barton-Davis","year":"1999","journal-title":"J Clin Invest"},{"key":"2024071611290067300_ljae063-B17","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1038\/nm1197-1280","article-title":"Suppression of a CFTR premature stop mutation in a bronchial epithelial cell line","volume":"3","author":"Bedwell","year":"1997","journal-title":"Nat Med"},{"key":"2024071611290067300_ljae063-B18","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1093\/hmg\/ddp030","article-title":"Translational readthrough by the aminoglycoside geneticin (G418) modulates SMN stability in vitro and improves motor function in SMA mice in vivo","volume":"18","author":"Heier","year":"2009","journal-title":"Hum Mol Genet"},{"key":"2024071611290067300_ljae063-B19","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1093\/hmg\/10.3.291","article-title":"Gentamicin-mediated suppression of Hurler syndrome stop mutations restores a low level of alpha-L-iduronidase activity and reduces lysosomal glycosaminoglycan accumulation","volume":"10","author":"Keeling","year":"2001","journal-title":"Hum Mol Genet"},{"key":"2024071611290067300_ljae063-B20","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1002\/ana.1023","article-title":"Gentamicin treatment of Duchenne and Becker muscular dystrophy due to nonsense mutations","volume":"49","author":"Wagner","year":"2001","journal-title":"Ann Neurol"},{"key":"2024071611290067300_ljae063-B21","doi-asserted-by":"crossref","first-page":"19483","DOI":"10.1073\/pnas.1312088110","article-title":"Repair of UV photolesions in xeroderma pigmentosum group C cells induced by translational readthrough of premature termination codons","volume":"110","author":"Kuschal","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2024071611290067300_ljae063-B22","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1038\/mt.2014.140","article-title":"Aminoglycosides restore full-length type VII collagen by overcoming premature termination codons: therapeutic implications for dystrophic epidermolysis bullosa","volume":"22","author":"Cogan","year":"2014","journal-title":"Mol Ther"},{"key":"2024071611290067300_ljae063-B23","doi-asserted-by":"crossref","first-page":"3028","DOI":"10.1172\/JCI92707","article-title":"Gentamicin induces functional type VII collagen in recessive dystrophic epidermolysis bullosa patients","volume":"127","author":"Woodley","year":"2017","journal-title":"J Clin Invest"},{"key":"2024071611290067300_ljae063-B24","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1741-7015-5-5","article-title":"In vitro prediction of stop-codon suppression by intravenous gentamicin in patients with cystic fibrosis: a pilot study","volume":"5","author":"Sermet-Gaudelus","year":"2007","journal-title":"BMC Med"},{"key":"2024071611290067300_ljae063-B25","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1177\/120347540100500202","article-title":"Measurement properties of Skindex-16: a brief quality-of-life measure for patients with skin diseases","volume":"5","author":"Chren","year":"2001","journal-title":"J Cutan Med Surg"},{"key":"2024071611290067300_ljae063-B26","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/j.1553-2712.2009.00620.x","article-title":"Validation of the Wong\u2013Baker FACES Pain Rating Scale in pediatric emergency department patients","volume":"17","author":"Garra","year":"2010","journal-title":"Acad Emerg Med"},{"key":"2024071611290067300_ljae063-B27","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/j.ymthe.2020.03.006","article-title":"Gentamicin induces laminin 332 and improves wound healing in junctional epidermolysis bullosa patients with nonsense mutations","volume":"28","author":"Kwong","year":"2020","journal-title":"Mol Ther"},{"key":"2024071611290067300_ljae063-B28","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1038\/jid.2013.475","article-title":"De novo anti-type VII collagen antibodies in patients with recessive dystrophic epidermolysis bullosa","volume":"134","author":"Woodley","year":"2014","journal-title":"J Invest Dermatol"},{"key":"2024071611290067300_ljae063-B29","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1172\/JCI113373","article-title":"Epidermolysis bullosa acquisita antigen is the globular carboxyl terminus of type VII procollagen","volume":"81","author":"Woodley","year":"1988","journal-title":"J Clin Invest"},{"key":"2024071611290067300_ljae063-B30","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1056\/NEJM198404193101602","article-title":"Identification of the skin basement-membrane autoantigen in epidermolysis bullosa acquisita","volume":"310","author":"Woodley","year":"1984","journal-title":"N Engl J Med"},{"key":"2024071611290067300_ljae063-B31","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jaad.2013.09.041","article-title":"Development, reliability, and validity of a novel Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI)","volume":"70","author":"Loh","year":"2014","journal-title":"J Am Acad Dermatol"},{"key":"2024071611290067300_ljae063-B32","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1111\/1523-1747.ep12265460","article-title":"Evaluation of anchoring fibrils and other components of the dermal-epidermal junction in dystrophic epidermolysis bullosa by a quantitative ultrastructural technique","volume":"84","author":"Tidman","year":"1985","journal-title":"J Invest Dermatol"},{"key":"2024071611290067300_ljae063-B33","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1038\/mt.2009.144","article-title":"Mechanisms of fibroblast cell therapy for dystrophic epidermolysis bullosa: high stability of collagen VII favors long-term skin integrity","volume":"17","author":"Kern","year":"2009","journal-title":"Mol Ther"},{"key":"2024071611290067300_ljae063-B34","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1111\/1523-1747.ep12365129","article-title":"Type VII collagen, anchoring fibrils, and epidermolysis bullosa","volume":"101","author":"Burgeson","year":"1993","journal-title":"J Invest Dermatol"},{"key":"2024071611290067300_ljae063-B35","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.jid.2016.02.002","article-title":"Collagen VII half-life at the dermal-epidermal junction zone: implications for mechanisms and therapy of genodermatoses","volume":"136","author":"K\u00fchl","year":"2016","journal-title":"J Invest Dermatol"},{"key":"2024071611290067300_ljae063-B36","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1111\/exd.14615","article-title":"T-cell activation and bacterial infection in skin wounds of recessive dystrophic epidermolysis bullosa patients","volume":"31","author":"Alexeev","year":"2022","journal-title":"Exp Dermatol"},{"key":"2024071611290067300_ljae063-B37","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1001\/jamadermatol.2021.5992","article-title":"Molecular and clinical outcomes after intravenous gentamicin treatment for patients with junctional epidermolysis bullosa caused by nonsense variants","volume":"158","author":"Mosallaei","year":"2022","journal-title":"JAMA Dermatol"}],"container-title":["British Journal of Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bjd\/advance-article-pdf\/doi\/10.1093\/bjd\/ljae063\/57096995\/ljae063.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bjd\/article-pdf\/191\/2\/267\/58554294\/ljae063.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bjd\/article-pdf\/191\/2\/267\/58554294\/ljae063.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T11:37:36Z","timestamp":1721129856000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bjd\/article\/191\/2\/267\/7609117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,16]]},"references-count":37,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,2,16]]},"published-print":{"date-parts":[[2024,7,16]]}},"URL":"https:\/\/doi.org\/10.1093\/bjd\/ljae063","relation":{},"ISSN":["0007-0963","1365-2133"],"issn-type":[{"value":"0007-0963","type":"print"},{"value":"1365-2133","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,8]]},"published":{"date-parts":[[2024,2,16]]}}}