{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:53:00Z","timestamp":1790837580648,"version":"4.1.0"},"reference-count":43,"publisher":"SAGE Publications","issue":"15-16","license":[{"start":{"date-parts":[[2020,8,1]],"date-time":"2020-08-01T00:00:00Z","timestamp":1596240000000},"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":[[2020,8]]},"abstract":"<jats:p>\n                    Friedreich's ataxia (FA), an autosomal recessive disorder caused by a deficiency in the expression of frataxin (FXN), is characterized by progressive ataxia and hypertrophic cardiomyopathy. Although cardiac dysfunction is the most common cause of mortality in FA, the cardiac disease remains subclinical for most of the clinical course because the neurologic disease limits muscle oxygen demands. Previous\n                    <jats:italic toggle=\"yes\">FXN<\/jats:italic>\n                    knockout mouse models exhibit fatal cardiomyopathy similar to human FA, but in contrast to the human condition, untreated mice become moribund by 2 months of age, unlike humans where the cardiac disease often does not manifest until the third decade. The study was designed to create a mouse model for early FA disease relevant to the time for which a gene therapy would likely be most effective. To generate a cardiac-specific mouse model of FA cardiomyopathy similar to the human disease, we used a cardiac promoter (\u03b1Myhc) driving CRE recombinase cardiac-specific excision of\n                    <jats:italic toggle=\"yes\">FXN<\/jats:italic>\n                    exon 4 to generate a mild, cardiac-specific FA model that is normal at rest, but exhibits the cardiac phenotype with stress. The hearts of \u03b1Myhc mice had decreased levels of FXN and activity of the mitochondrial complex II\/complex IV respiratory chain. At rest, \u03b1Myhc mice exhibited normal cardiac function as assessed by echocardiographic assessment of ejection fraction and fractional shortening, but when the heart was stressed chemically with dobutamine, \u03b1Myhc mice compared with littermate control mice had a 62% reduction in the stress ejection fraction (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009&lt;\u20092\u2009\u00d7\u200910\n                    <jats:sup>\u22124<\/jats:sup>\n                    ) and 71% reduction in stress-related fractional shortening (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009&lt;\u200910\n                    <jats:sup>\u22125<\/jats:sup>\n                    ). When assessing functional cardiac performance using running on an inclined treadmill, \u03b1Myhc mice stayed above the midline threefold less than littermate controls (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009&lt;\u20090.02). A one-time intravenous administration of 10\n                    <jats:sup>11<\/jats:sup>\n                    genome copies of AAVrh.10hFXN, an adeno-associated virus (AAV) serotype rh10 gene transfer vector expressing human\n                    <jats:italic toggle=\"yes\">FXN<\/jats:italic>\n                    , corrected the stress-induced ejection fraction and fractional shortening phenotypes. Treated \u03b1Myhc mice exhibited exercise performance on a treadmill indistinguishable from littermate controls (\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009&gt;\u20090.07). These \u03b1Myhc mice provide an ideal model to study long-term cardiac complications due to FA and AAV-mediated gene therapy correction of stress-induced cardiac phenotypes typical of human FA.\n                  <\/jats:p>","DOI":"10.1089\/hum.2019.363","type":"journal-article","created":{"date-parts":[[2020,7,10]],"date-time":"2020-07-10T00:44:33Z","timestamp":1594341873000},"page":"819-827","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":37,"title":["Stress-Induced Mouse Model of the Cardiac Manifestations of Friedreich's Ataxia Corrected by AAV-mediated Gene Therapy"],"prefix":"10.1177","volume":"31","author":[{"given":"Christiana O.","family":"Salami","sequence":"first","affiliation":[{"name":"Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clarisse","family":"Jose","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laith","family":"Alyass","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges-Ibrahim","family":"Cisse","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bishnu P.","family":"De","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie M.","family":"Stiles","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J.","family":"Chiuchiolo","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dolan","family":"Sondhi","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald G.","family":"Crystal","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Kaminsky","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,8,17]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2011.01.010"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12470"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4914(02)02330-4"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12220"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.06.030"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.2.275"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.37.1.1"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1177\/0883073812448535"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ncl.2013.05.002"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD007791.pub4"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1177\/0883073812448230"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.12928"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehq443"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2011.05.023"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/ejechocard\/jer267"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.059477"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-405195-9.00065-2"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3510"},{"key":"e_1_3_6_20_2","first-page":"A158","article-title":"Feasibility of gene therapy for Friedreich Ataxia-associated cardiomyopathy in non-human primates","volume":"30","author":"Belbellaa B","year":"2019","unstructured":"Belbellaa B, , Bonnamain V, , Kaminsky SM, et al. Feasibility of gene therapy for Friedreich Ataxia-associated cardiomyopathy in non-human primates. Hum Gene Ther, 2019; 30:A158\u2013A159.","journal-title":"Hum Gene Ther"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy427"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/jgm.1496"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0029(20000915)50:6<522::AID-JEMT9>3.0.CO;2-U"},{"key":"e_1_3_6_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(91)90434-D"},{"key":"e_1_3_6_25_2","doi-asserted-by":"publisher","DOI":"10.1089\/10430349950019219"},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302549"},{"key":"e_1_3_6_27_2","doi-asserted-by":"publisher","DOI":"10.1089\/hgtb.2017.246"},{"key":"e_1_3_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2006.05.011"},{"key":"e_1_3_6_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/104.3.589"},{"key":"e_1_3_6_30_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-015-0439-z"},{"key":"e_1_3_6_31_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199610173351601"},{"key":"e_1_3_6_32_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.65.10.1296"},{"key":"e_1_3_6_33_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2015.1855"},{"key":"e_1_3_6_34_2","doi-asserted-by":"publisher","DOI":"10.4330\/wjc.v11.i1.1"},{"key":"e_1_3_6_35_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.31.1.5"},{"key":"e_1_3_6_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.95.9.2247"},{"key":"e_1_3_6_37_2","first-page":"167","article-title":"Cardiomyopathy in patients with friedreich's ataxia\u2014appearance and diagnostic value","volume":"3","author":"Schmidinger S","year":"2000","unstructured":"Schmidinger S, , Eiber J, , Schols L, et al. Cardiomyopathy in patients with friedreich's ataxia\u2014appearance and diagnostic value. J Clin Basic Cardiol, 2000; 3:167\u2013171.","journal-title":"J Clin Basic Cardiol"},{"key":"e_1_3_6_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00242-2"},{"key":"e_1_3_6_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ppedcard.2011.02.007"},{"key":"e_1_3_6_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24248"},{"key":"e_1_3_6_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12219"},{"key":"e_1_3_6_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/84818"},{"key":"e_1_3_6_43_2","doi-asserted-by":"publisher","DOI":"10.1007\/s100480100118"},{"key":"e_1_3_6_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2006.06.015"}],"container-title":["Human Gene Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/hum.2019.363","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/hum.2019.363","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/hum.2019.363","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:55:15Z","timestamp":1777449315000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/hum.2019.363"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8]]},"references-count":43,"journal-issue":{"issue":"15-16","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["10.1089\/hum.2019.363"],"URL":"https:\/\/doi.org\/10.1089\/hum.2019.363","relation":{},"ISSN":["1043-0342","1557-7422"],"issn-type":[{"value":"1043-0342","type":"print"},{"value":"1557-7422","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8]]}}}