Faculty, Staff and Student Publications
Publication Date
3-1-2025
Journal
Journal of Inherited Metabolic Disease
DOI
10.1002/jimd.70014
PMID
40064185
PMCID
PMC11893205
PubMedCentral® Posted Date
5-10-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Glycogen storage disease type Ia (GSDIa) is a rare, life‐threatening, inherited carbohydrate metabolism disorder caused by glucose‐6‐phosphatase (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‐associated virus serotype 8 vector expressing the human G6PC1 gene that encodes G6Pase. This open‐label, phase 1/2, dose‐escalation, 52‐week 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 × 1012 genome copies (GC)/kg, and three participants each in Cohorts 2, 3, and 4 received 6.0 × 1012 GC/kg. Corticosteroids were administered to mitigate vector‑induced inflammatory response. All participants experienced a treatment‐emergent adverse event (TEAE) and a related TEAE. No participant experienced a dose‐limiting toxicity, TEAE leading to study discontinuation, TEAE leading to death, or serious treatment‐related 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 52, a mean (SD) increase of 46% (72%). Mean total daily cornstarch intake was 284 g at baseline and 85 g 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%); p < 0.001. 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.
Keywords
Humans, Genetic Therapy, Glycogen Storage Disease Type I, Adult, Male, Female, Dependovirus, Middle Aged, Genetic Vectors, Liver, Glucose-6-Phosphatase, Young Adult, Treatment Outcome, Adolescent
Published Open-Access
yes
Recommended Citation
Weinstein, David A; Derks, Terry G; Rodriguez-Buritica, David F; et al., "Safety and Efficacy of DTX401, an AAV8-Mediated Liver-Directed Gene Therapy, in Adults With Glycogen Storage Disease Type I a (GSDIa)" (2025). Faculty, Staff and Student Publications. 6468.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6468
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