{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:30:37Z","timestamp":1790400637053,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,6,30]],"date-time":"2015-06-30T00:00:00Z","timestamp":1435622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005202","name":"MUSCULAR DYSTROPHY ASSOCIATION","doi-asserted-by":"crossref","award":["MDA 277250"],"award-info":[{"award-number":["MDA 277250"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>X\u2010linked Charcot\u2013Marie\u2013Tooth disease (CMT1X) is a common inherited neuropathy caused by mutations in the <jats:italic>GJB1<\/jats:italic> gene encoding the gap junction protein connexin32 (Cx32). Clinical studies and disease models indicate that neuropathy mainly results from Schwann cell autonomous, loss\u2010of\u2010function mechanisms; therefore, CMT1X may be treatable by gene replacement.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A lentiviral vector LV.<jats:italic>Mpz\u2010GJB1<\/jats:italic> carrying the <jats:italic>GJB1<\/jats:italic> gene under the Schwann cell\u2013specific myelin protein zero (<jats:italic>Mpz<\/jats:italic>) promoter was generated and delivered into the mouse sciatic nerve by a single injection immediately distal to the sciatic notch. Enhanced green fluorescent protein (EGFP) reporter gene expression was quantified and Cx32 expression was examined on a Cx32 knockout (KO) background. A gene therapy trial was performed in a Cx32 KO model of CMT1X.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>EGFP was expressed throughout the length of the sciatic nerve in up to 50% of Schwann cells starting 2 weeks after injection and remaining stable for up to 16 weeks. Following LV.<jats:italic>Mpz\u2010GJB1<\/jats:italic> injection into Cx32 KO nerves, we detected Cx32 expression and correct localization in non\u2013compact myelin areas where gap junctions are normally formed. Gene therapy trial by intraneural injection in groups of 2\u2010month\u2010old Cx32 KO mice, before demyelination onset, significantly reduced the ratio of abnormally myelinated fibers (<jats:italic>p<\/jats:italic>\u2009=\u20090.00148) and secondary inflammation (<jats:italic>p<\/jats:italic>\u2009=\u20090.0178) at 6 months of age compared to mock\u2010treated animals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Gene delivery using a lentiviral vector leads to efficient gene expression specifically in Schwann cells. Restoration of Cx32 expression ameliorates nerve pathology in a disease model and provides a promising approach for future treatments of CMT1X and other inherited neuropathies. 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