{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T02:40:21Z","timestamp":1793932821727,"version":"4.8.0"},"reference-count":38,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T00:00:00Z","timestamp":1705536000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy - Methods & Clinical Development"],"published-print":{"date-parts":[[2024,3]]},"DOI":"10.1016\/j.omtm.2024.101193","type":"journal-article","created":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T12:12:14Z","timestamp":1705925534000},"page":"101193","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":23,"title":["AAV8 gene therapy reverses cardiac pathology and prevents early mortality in a mouse model of Friedreich\u2019s ataxia"],"prefix":"10.1016","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-8541-5763","authenticated-orcid":false,"given":"Joshua C.","family":"Chang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Molly R.","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie C.","family":"Stark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pravinkumar","family":"Purushothaman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fria","family":"Bolan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin A.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Champe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Lawlor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Halawani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie V.","family":"Ngaba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Lynch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Gonzalo-Gil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathleen","family":"Lutz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizia","family":"Urbinati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bala","family":"Medicherla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0680-6456","authenticated-orcid":false,"given":"Carlos","family":"Fonck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.omtm.2024.101193_bib1","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1126\/science.271.5254.1423","article-title":"Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion","volume":"271","author":"Campuzano","year":"1996","journal-title":"Science"},{"key":"10.1016\/j.omtm.2024.101193_bib2","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1002\/acn3.225","article-title":"Frataxin levels in peripheral tissue in Friedreich ataxia","volume":"2","author":"Lazaropoulos","year":"2015","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"10.1016\/j.omtm.2024.101193_bib3","doi-asserted-by":"crossref","DOI":"10.1042\/NS20180060","article-title":"Role of frataxin protein deficiency and metabolic dysfunction in Friedreich ataxia, an autosomal recessive mitochondrial disease","volume":"2","author":"Clark","year":"2018","journal-title":"Neuronal Signal."},{"key":"10.1016\/j.omtm.2024.101193_bib4","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1111\/bph.12470","article-title":"Fixing frataxin: \u2018ironing out\u2019 the metabolic defect in Friedreich's ataxia","volume":"171","author":"Anzovino","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.omtm.2024.101193_bib5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jns.2011.01.010","article-title":"Friedreich's ataxia: pathology, pathogenesis, and molecular genetics","volume":"303","author":"Koeppen","year":"2011","journal-title":"J.\u00a0Neurol. Sci."},{"key":"10.1016\/j.omtm.2024.101193_bib6","doi-asserted-by":"crossref","first-page":"7452","DOI":"10.1073\/pnas.94.14.7452","article-title":"Evolution of the Friedreich's ataxia trinucleotide repeat expansion: founder effect and premutations","volume":"94","author":"Coss\u00e9e","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.omtm.2024.101193_bib7","doi-asserted-by":"crossref","DOI":"10.1016\/j.nbd.2019.104606","article-title":"Friedreich ataxia- pathogenesis and implications for therapies","volume":"132","author":"Delatycki","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.omtm.2024.101193_bib8","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1093\/brain\/104.3.589","article-title":"Friedreich's ataxia: a clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features","volume":"104","author":"Harding","year":"1981","journal-title":"Brain"},{"key":"10.1016\/j.omtm.2024.101193_bib9","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.jns.2011.05.023","article-title":"Mortality in Friedreich ataxia","volume":"307","author":"Tsou","year":"2011","journal-title":"J.\u00a0Neurol. Sci."},{"key":"10.1016\/j.omtm.2024.101193_bib10","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0116396","article-title":"The pathogenesis of cardiomyopathy in Friedreich ataxia","volume":"10","author":"Koeppen","year":"2015","journal-title":"PLoS One"},{"issue":"Suppl 1","key":"10.1016\/j.omtm.2024.101193_bib11","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/jnc.12217","article-title":"Cardiomyopathy of Friedreich ataxia","volume":"126","author":"Weidemann","year":"2013","journal-title":"J.\u00a0Neurochem."},{"key":"10.1016\/j.omtm.2024.101193_bib12","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.3390\/ijms22041815","article-title":"Future prospects of gene therapy for Friedreich's ataxia","volume":"22","author":"Ocana-Santero","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.omtm.2024.101193_bib13","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1038\/nm.3510","article-title":"Prevention and reversal of severe mitochondrial cardiomyopathy by gene therapy in a mouse model of Friedreich's ataxia","volume":"20","author":"Perdomini","year":"2014","journal-title":"Nat. Med."},{"key":"10.1016\/j.omtm.2024.101193_bib14","doi-asserted-by":"crossref","DOI":"10.1038\/mtm.2014.44","article-title":"An AAV9 coding for frataxin clearly improved the symptoms and prolonged the life of Friedreich ataxia mouse models","volume":"1","author":"G\u00e9rard","year":"2014","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.omtm.2024.101193_bib15","doi-asserted-by":"crossref","first-page":"1940","DOI":"10.1016\/j.ymthe.2018.05.006","article-title":"Rapid and complete reversal of sensory ataxia by gene therapy in a novel model of Friedreich ataxia","volume":"26","author":"Piguet","year":"2018","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2024.101193_bib16","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0063958","article-title":"Development of frataxin gene expression measures for the evaluation of experimental treatments in Friedreich's ataxia","volume":"8","author":"Plasterer","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.omtm.2024.101193_bib17","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.omtm.2020.08.018","article-title":"High levels of frataxin overexpression lead to mitochondrial and cardiac toxicity in mouse models","volume":"19","author":"Belbellaa","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.omtm.2024.101193_bib18","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.omtm.2022.02.002","article-title":"In\u00a0vivo overexpression of frataxin causes toxicity mediated by iron-sulfur cluster deficiency","volume":"24","author":"Huichalaf","year":"2022","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.omtm.2024.101193_bib19","article-title":"Adding a temporal dimension to the study of Friedreich's ataxia: the effect of frataxin overexpression in a human cell model","volume":"11","author":"Vannocci","year":"2018","journal-title":"Dis. Model. Mech."},{"key":"10.1016\/j.omtm.2024.101193_bib20","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0010611","article-title":"Systematic comparison of constitutive promoters and the doxycycline-inducible promoter","volume":"5","author":"Qin","year":"2010","journal-title":"PLoS One"},{"key":"10.1016\/j.omtm.2024.101193_bib21","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/84818","article-title":"Mouse models for Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits","volume":"27","author":"Puccio","year":"2001","journal-title":"Nat. Genet."},{"key":"10.1016\/j.omtm.2024.101193_bib22","first-page":"175","article-title":"The adeno-associated virus genome packaging puzzle","volume":"9","author":"Ling","year":"2015","journal-title":"J.\u00a0Mol. Genet. Med."},{"key":"10.1016\/j.omtm.2024.101193_bib23","doi-asserted-by":"crossref","DOI":"10.1016\/j.jim.2019.07.001","article-title":"Evaluation of antibodies for western blot analysis of frataxin protein isoforms","volume":"474","author":"Weng","year":"2019","journal-title":"J.\u00a0Immunol. Methods"},{"key":"10.1016\/j.omtm.2024.101193_bib24","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-020-72884-w","article-title":"Extra-mitochondrial mouse frataxin and its implications for mouse models of Friedreich's ataxia","volume":"10","author":"Weng","year":"2020","journal-title":"Sci. Rep."},{"key":"10.1016\/j.omtm.2024.101193_bib25","doi-asserted-by":"crossref","first-page":"3521","DOI":"10.1093\/hmg\/ddn244","article-title":"The in\u00a0vivo mitochondrial two-step maturation of human frataxin","volume":"17","author":"Schmucker","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.omtm.2024.101193_bib26","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.ppedcard.2011.02.007","article-title":"The heart in Friedreich's ataxia: basic findings and clinical implications","volume":"31","author":"Payne","year":"2011","journal-title":"Prog. Pediatr. Cardiol."},{"key":"10.1016\/j.omtm.2024.101193_bib27","first-page":"319","article-title":"Body condition scoring: a rapid and accurate method for assessing health status in mice","volume":"49","author":"Ullman-Culler\u00e9","year":"1999","journal-title":"Lab. Anim. Sci."},{"key":"10.1016\/j.omtm.2024.101193_bib28","doi-asserted-by":"crossref","first-page":"75","DOI":"10.3389\/fnins.2019.00075","article-title":"The role of iron in Friedreich's ataxia: insights from studies in human tissues and cellular and animal models","volume":"13","author":"Llorens","year":"2019","journal-title":"Front. Neurosci."},{"key":"10.1016\/j.omtm.2024.101193_bib29","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1038\/mt.2008.76","article-title":"Analysis of AAV serotypes 1-9 mediated gene expression and tropism in mice after systemic injection","volume":"16","author":"Zincarelli","year":"2008","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2024.101193_bib30","article-title":"AAV-mediated gene therapy: Advancing cardiovascular disease treatment","volume":"9","author":"Zhang","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"10.1016\/j.omtm.2024.101193_bib31","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1089\/hum.2009.182","article-title":"Prevalence of serum IgG and neutralizing factors against adeno-associated virus (AAV) types 1, 2, 5, 6, 8, and 9 in the healthy population: implications for gene therapy using AAV vectors","volume":"21","author":"Boutin","year":"2010","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.omtm.2024.101193_bib32","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1161\/CIRCULATIONAHA.112.095364","article-title":"Cardiomyopathy in Friedreich ataxia: exemplifying the challenges faced by cardiologists in the management of rare diseases","volume":"125","author":"Jensen","year":"2012","journal-title":"Circulation"},{"key":"10.1016\/j.omtm.2024.101193_bib33","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0016199","article-title":"Mammalian frataxin: an essential function for cellular viability through an interaction with a preformed ISCU\/NFS1\/ISD11 iron-sulfur assembly complex","volume":"6","author":"Schmucker","year":"2011","journal-title":"PLoS One"},{"key":"10.1016\/j.omtm.2024.101193_bib34","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1093\/hmg\/9.8.1219","article-title":"Inactivation of the Friedreich ataxia mouse gene leads to early embryonic lethality without iron accumulation","volume":"9","author":"Coss\u00e9e","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.omtm.2024.101193_bib35","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1093\/hmg\/6.11.1771","article-title":"Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes","volume":"6","author":"Campuzano","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.omtm.2024.101193_bib36","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1089\/hum.2023.020","article-title":"Identification of safe and effective intravenous dose of AAVrh.10hFXN to treat the cardiac manifestations of Friedreich's ataxia","volume":"34","author":"Munoz-Zuluaga","year":"2023","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.omtm.2024.101193_bib37","doi-asserted-by":"crossref","first-page":"9757","DOI":"10.1073\/pnas.0804261105","article-title":"The MCK mouse heart model of Friedreich's ataxia: alterations in iron-regulated proteins and cardiac hypertrophy are limited by iron chelation","volume":"105","author":"Whitnall","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.omtm.2024.101193_bib38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4330\/wjc.v11.i1.1","article-title":"Heart disease in Friedreich's ataxia","volume":"11","author":"Hanson","year":"2019","journal-title":"World J. Cardiol."}],"container-title":["Molecular Therapy - Methods & Clinical Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2329050124000093?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2329050124000093?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,7,27]],"date-time":"2024-07-27T13:13:56Z","timestamp":1722086036000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2329050124000093"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["S2329050124000093"],"URL":"https:\/\/doi.org\/10.1016\/j.omtm.2024.101193","relation":{},"ISSN":["2329-0501"],"issn-type":[{"value":"2329-0501","type":"print"}],"subject":[],"published":{"date-parts":[[2024,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"AAV8 gene therapy reverses cardiac pathology and prevents early mortality in a mouse model of Friedreich\u2019s ataxia","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy - Methods & Clinical Development","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.omtm.2024.101193","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Authors.","name":"copyright","label":"Copyright"}],"article-number":"101193"}}