{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:55:45Z","timestamp":1791896145644,"version":"4.3.4"},"reference-count":61,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T00:00:00Z","timestamp":1546992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["680766"],"award-info":[{"award-number":["680766"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["GGP15004"],"award-info":[{"award-number":["GGP15004"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002243","name":"National Ataxia Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002243","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Friedreich's ataxia is an autosomal\u2010recessive cerebellar ataxia caused by mutation of the frataxin gene, resulting in decreased frataxin expression, mitochondrial dysfunction, and oxidative stress. Currently, no treatment is available for Friedreich's ataxia patients. Given that levels of residual frataxin critically affect disease severity, the main goal of a specific therapy for Friedreich's ataxia is to increase frataxin levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>With the aim to accelerate the development of a new therapy for Friedreich's ataxia, we took a drug repositioning approach to identify market\u2010available drugs able to increase frataxin levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using a cell\u2010based reporter assay to monitor variation in frataxin amount, we performed a high\u2010throughput screening of a library containing 853 U.S. Food and Drug Administration\u2013approved drugs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the potentially interesting candidates isolated from the screening, we focused our attention on etravirine, an antiviral drug currently in use as an anti\u2013human immunodeficiency virus therapy. Here, we show that etravirine can promote a significant increase in frataxin levels in cells derived from Friedreich's ataxia patients, by enhancing frataxin messenger RNA translation. Importantly, frataxin accumulation in treated patient cell lines is comparable to frataxin levels in unaffected carrier cells, suggesting that etravirine could be therapeutically relevant. Indeed, etravirine treatment restores the activity of the iron\u2010sulphur cluster containing enzyme aconitase and confers resistance to oxidative stress in cells derived from Friedreich's ataxia patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Considering its excellent safety profile along with its ability to increase frataxin levels and correct some of the disease\u2010related defects, etravirine represents a promising candidate as a therapeutic for Friedreich's ataxia. \u00a9 2019 International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.27604","type":"journal-article","created":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T10:33:34Z","timestamp":1547030014000},"page":"323-334","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Drug repositioning screening identifies etravirine as a potential therapeutic for friedreich's ataxia"],"prefix":"10.1002","volume":"34","author":[{"given":"Giulia","family":"Alfedi","sequence":"first","affiliation":[{"name":"Laboratory of Signal Transduction, Department of Biomedicine and Prevention University of Rome \u201cTor Vergata\u201d  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Luffarelli","sequence":"additional","affiliation":[{"name":"Laboratory of Signal Transduction, Department of Biomedicine and Prevention University of Rome \u201cTor Vergata\u201d  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivano","family":"Cond\u00f2","sequence":"additional","affiliation":[{"name":"Laboratory of Signal Transduction, Department of Biomedicine and Prevention University of Rome \u201cTor Vergata\u201d  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Pedini","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurobiology, Department of Biomedicine and Prevention University of Rome \u201cTor Vergata\u201d  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Mannucci","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurobiology, Department of Biomedicine and Prevention University of Rome \u201cTor Vergata\u201d  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damiano S.","family":"Massaro","sequence":"additional","affiliation":[{"name":"Laboratory of Signal Transduction, Department of Biomedicine and Prevention University of Rome \u201cTor Vergata\u201d  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Benini","sequence":"additional","affiliation":[{"name":"Laboratory of Signal Transduction, Department of Biomedicine and Prevention University of Rome \u201cTor Vergata\u201d  Rome Italy"},{"name":"Fratagene Therapeutics Srl  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Toschi","sequence":"additional","affiliation":[{"name":"Medical Physics Section, Department of Biomedicine and Prevention University of Rome \u201cTor Vergata\u201d  Rome Italy"},{"name":"Department of Radiology Athinoula A. 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