{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T07:29:26Z","timestamp":1787124566035,"version":"build-2736575974"},"reference-count":23,"publisher":"SAGE Publications","issue":"3-4","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100014943","name":"Sarepta Therapeutics","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100014943","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2026,2,1]]},"abstract":"<jats:p>\n                    Limb-girdle muscular dystrophy type 2E\/R4 (LGMD2E\/R4) is an ultra-rare autosomal recessive disorder caused by mutations in\n                    <jats:italic toggle=\"yes\">SGCB<\/jats:italic>\n                    , the gene that encodes for \u03b2-sarcoglycan (SGCB), a component of the dystrophin-associated protein complex that stabilizes muscle fibers during contractions. Bidridistrogene xeboparvovec is an investigational adeno-associated virus-mediated gene transfer therapy designed to deliver a codon-optimized, full-length human\n                    <jats:italic toggle=\"yes\">SGCB<\/jats:italic>\n                    and induce targeted expression of functional human SGCB protein. Interim safety and efficacy data from a clinical trial in patients with LGDM2E\/R4 aged 4\u201315 years (NCT03652259) support further clinical development of bidridistrogene xeboparvovec. However, less is known about the effects of this agent in patients with more advanced LGMD2E\/R4, who on average are older and heavier, which prompted their inclusion in studies VOYAGENE (NCT05876780, phase 1) and EMERGENE (NCT06246513, phase 3). In the preclinical study presented here, we delivered bidridistrogene xeboparvovec (0.185 \u00d7 10\n                    <jats:sup>13<\/jats:sup>\n                    vg\/kg, 0.37 \u00d7 10\n                    <jats:sup>13<\/jats:sup>\n                    vg\/kg, 0.74 \u00d7 10\n                    <jats:sup>13<\/jats:sup>\n                    vg\/kg, 1.85 \u00d7 10\n                    <jats:sup>13<\/jats:sup>\n                    vg\/kg, or 7.4 \u00d7 10\n                    <jats:sup>13<\/jats:sup>\n                    vg\/kg) to\n                    <jats:italic toggle=\"yes\">Sgcb<\/jats:italic>\n                    -\/- mice aged 27\u201342 weeks (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 4 per dose) with age-matched saline-treated\n                    <jats:italic toggle=\"yes\">Sgcb-\/-<\/jats:italic>\n                    and C57BL\/6J mice used as controls. Approximately 12 weeks after administration, we observed SGCB expression and found evidence of reduction in muscle fibrosis, reduction in muscle damage, and restoration of muscle force. Overall, a dose-dependent increase in vector exposure across tissue types was observed, with a nonlinear, exposure-dependent increase in both SGCB expression and functional improvement that reached saturation at 7.4 \u00d7 10\n                    <jats:sup>13<\/jats:sup>\n                    vg\/kg. Pharmacokinetic and pharmacodynamic analyses demonstrated a robust relationship between vector biodistribution, SGCB expression, and muscle force, further supporting clinical development of bidridistrogene xeboparvovec at the highest dose (7.4 \u00d7 10\n                    <jats:sup>13<\/jats:sup>\n                    vg\/kg), across a broad LGMD2E\/R4 population and regardless of disease progression.\n                  <\/jats:p>","DOI":"10.1177\/10430342251393700","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T08:11:21Z","timestamp":1762416681000},"page":"93-101","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetic and Pharmacodynamic Evaluation of Bidridistrogene Xeboparvovec in an Aged Murine Model of Limb-Girdle Muscular Dystrophy Type 2E\/R4"],"prefix":"10.1177","volume":"37","author":[{"given":"Stephen","family":"Baine","sequence":"first","affiliation":[{"name":"Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared","family":"Cui","sequence":"additional","affiliation":[{"name":"Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Eun","family":"Seo","sequence":"additional","affiliation":[{"name":"Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber","family":"Kempton","sequence":"additional","affiliation":[{"name":"Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Rogers","sequence":"additional","affiliation":[{"name":"Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Haile","sequence":"additional","affiliation":[{"name":"Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlin","family":"Adegboye","sequence":"additional","affiliation":[{"name":"Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine","family":"Wu","sequence":"additional","affiliation":[{"name":"Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Lemmerman","sequence":"additional","affiliation":[{"name":"Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Guerrero","sequence":"additional","affiliation":[{"name":"Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitlin","family":"Jones","sequence":"additional","affiliation":[{"name":"Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Mayes","sequence":"additional","affiliation":[{"name":"Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tesla","family":"Freehafer","sequence":"additional","affiliation":[{"name":"Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Lewis","sequence":"additional","affiliation":[{"name":"Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Pozsgai","sequence":"additional","affiliation":[{"name":"Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilly","family":"East","sequence":"additional","affiliation":[{"name":"Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Rodino-Klapac","sequence":"additional","affiliation":[{"name":"Sarepta Therapeutics, Inc., Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael","family":"Potter","sequence":"additional","affiliation":[{"name":"Sarepta Therapeutics, Inc., Cambridge, Massachusetts, 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