{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:09:59Z","timestamp":1790622599921,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Progressive loss of muscle and muscle function is associated with significant fibrosis in Duchenne muscular dystrophy (DMD) patients. Halofuginone, an analog of febrifugine, prevents fibrosis in various animal models, including those of muscular dystrophies. Effects of (+)\/(\u2212)-halofuginone enantiomers on motor coordination and diaphragm histopathology in mdx mice, the mouse model for DMD, were examined. Four-week-old male mice were treated with racemic halofuginone, or its separate enantiomers, for 10 weeks. Controls were treated with saline. Racemic halofuginone-treated mice demonstrated better motor coordination and balance than controls. However, (+)-halofuginone surpassed the racemic form\u2019s effect. No effect was observed for (\u2212)-halofuginone, which behaved like the control. A significant reduction in collagen content and degenerative areas, and an increase in utrophin levels were observed in diaphragms of mice treated with racemic halofuginone. Again, (+)-halofuginone was more effective than the racemic form, whereas (\u2212)-halofuginone had no effect. Both racemic and (+)-halofuginone increased diaphragm myofiber diameters, with no effect for (\u2212)-halofuginone. No effects were observed for any of the compounds tested in an in-vitro cell viability assay. These results, demonstrating a differential effect of the halofuginone enantiomers and superiority of (+)-halofuginone, are of great importance for future use of (+)-halofuginone as a DMD antifibrotic therapy.<\/jats:p>","DOI":"10.3390\/ijms22137063","type":"journal-article","created":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T10:03:19Z","timestamp":1625047399000},"page":"7063","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Differential Effects of Halofuginone Enantiomers on Muscle Fibrosis and Histopathology in Duchenne Muscular Dystrophy"],"prefix":"10.3390","volume":"22","author":[{"given":"Sharon","family":"Mordechay","sequence":"first","affiliation":[{"name":"Department of Animal Sciences, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot 76100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaun","family":"Smullen","sequence":"additional","affiliation":[{"name":"Center for Synthesis and Chemical Biology, School of Chemistry, University College Dublin, D04 N2E5 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Evans","sequence":"additional","affiliation":[{"name":"Center for Synthesis and Chemical Biology, School of Chemistry, University College Dublin, D04 N2E5 Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Genin","sequence":"additional","affiliation":[{"name":"The Volcani Center, Institute of Animal Science, Bet Dagan 52505, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Pines","sequence":"additional","affiliation":[{"name":"The Volcani Center, Institute of Animal Science, Bet Dagan 52505, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orna","family":"Halevy","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences, The Hebrew University of Jerusalem, P.O. Box 12, Rehovot 76100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"273","DOI":"10.3109\/03008208509152408","article-title":"Fibronectin, laminin, type I, III and IV collagens in Duchenne\u2019s muscular dystrophy, congenital muscular dystrophies and congenital myopathies: An immunocytochemical study","volume":"13","author":"Hantai","year":"1985","journal-title":"Connect. Tissue Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.ajpath.2012.11.004","article-title":"The involvement of Collagen triple helix repeat containing 1 in muscular dystrophies","volume":"182","author":"Spector","year":"2013","journal-title":"Am. J. 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