{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:00:57Z","timestamp":1791943257910,"version":"4.3.4"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T00:00:00Z","timestamp":1741564800000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013220","name":"Ultragenyx Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013220","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Glycogen storage disease type Ia (GSDIa) is a rare, life\u2010threatening, inherited carbohydrate metabolism disorder caused by glucose\u20106\u2010phosphatase (G6Pase) deficiency, which is essential for glycogenolysis and gluconeogenesis. GSDIa management includes a strict medically prescribed diet that typically includes daily uncooked cornstarch doses, including overnight, to maintain euglycemia. DTX401 is an investigational adeno\u2010associated virus serotype 8 vector expressing the human\n                    <jats:italic>G6PC1<\/jats:italic>\n                    gene that encodes G6Pase. This open\u2010label, phase 1\/2, dose\u2010escalation, 52\u2010week gene therapy trial evaluated the safety and efficacy of a single DTX401 infusion in 12 adults with GSDIa (ClinicalTrials.gov Identifier: NCT03517085). Three participants in Cohort 1 received DTX401 2.0\u2009\u00d7\u200910\n                    <jats:sup>12<\/jats:sup>\n                    genome copies (GC)\/kg, and three participants each in Cohorts 2, 3, and 4 received 6.0\u2009\u00d7\u200910\n                    <jats:sup>12<\/jats:sup>\n                    GC\/kg. Corticosteroids were administered to mitigate vector\u2011induced inflammatory response. All participants experienced a treatment\u2010emergent adverse event (TEAE) and a related TEAE. No participant experienced a dose\u2010limiting toxicity, TEAE leading to study discontinuation, TEAE leading to death, or serious treatment\u2010related TEAE. Mean (SD) time to hypoglycemia in minutes\/gram of carbohydrate during a controlled fasting challenge was 5.0 (1.6) at baseline and 6.9 (2.7) at Week\u200952, a mean (SD) increase of 46% (72%). Mean total daily cornstarch intake was 284\u2009g at baseline and 85\u2009g at Week 52 in the 10 participants with available values at both time points, a mean (SD) total daily cornstarch intake reduction of 68% (20%);\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001. DTX401 showed a favorable safety and efficacy profile at Week 52. Participants in all cohorts showed significant cornstarch need reductions from baseline to Week 52.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70014","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T20:22:30Z","timestamp":1741724550000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Safety and Efficacy of\n                    <scp>DTX401<\/scp>\n                    , an\n                    <scp>AAV8<\/scp>\n                    \u2010Mediated Liver\u2010Directed Gene Therapy, in Adults With Glycogen Storage Disease Type I a (\n                    <scp>GSDIa<\/scp>\n                    )"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1341-9367","authenticated-orcid":false,"given":"David A.","family":"Weinstein","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of Connecticut  Farmington Connecticut 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