ArticleHepatology (Baltimore, Md.)2012
Prevention of hepatocellular adenoma and correction of metabolic abnormalities in murine glycogen storage disease type Ia by gene therapy.
Article in Hepatology (Baltimore, Md.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 85 citations in OpenAlex.
- Safety and Efficacy of DTX401, an AAV8-Mediated Liver-Directed Gene Therapy, in Adults With Glycogen Storage Disease Type I a (GSDIa).Journal of inherited metabolic disease · 2025Trial
- Successful surgical management of multiple hepatocellular adenomas in a young female patient with glycogen storage disease type Ia: a case report.Journal of medical case reports · 2026Article
- Untargeted Proteomics Profiling of Liver and Plasma in Fed and Fasted Liver-Specific Glycogen Storage Disease Type Ia (GSD Ia) Mice: Toward Potential Protein Biomarkers.Journal of inherited metabolic disease · 2026Article
- Liver-directed AAV gene therapy in mice corrects glycogen storage disease type IX γ2.Science advances · 2025Article
- Article
- Liver-Directed Gene Therapy Mitigates Early Nephropathy in Murine Glycogen Storage Disease Type Ia.Journal of inherited metabolic disease · 2025Article
- Recent developments in translational imaging of in vivo gene therapy outcomes.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Impaired Glucose Metabolism, Primary Cilium Defects, and Kidney Cystogenesis in Glycogen Storage Disease Type Ia.Journal of the American Society of Nephrology : JASN · 2024Article
- Base-editing corrects metabolic abnormalities in a humanized mouse model for glycogen storage disease type-Ia.Nature communications · 2024Article
- Gene therapy for glycogen storage diseases.Journal of inherited metabolic disease · 2024Review
- A splice-switching oligonucleotide treatment ameliorates glycogen storage disease type 1a in mice with G6PC c.648G>T.The Journal of clinical investigation · 2023Article
- CRISPR/Cas9-based double-strand oligonucleotide insertion strategy corrects metabolic abnormalities in murine glycogen storage disease type-Ia.Journal of inherited metabolic disease · 2023Article
- Genome editing usingMolecular therapy. Methods & clinical development · 2023Article
- Glycogen storage disease type I: Genetic etiology, clinical manifestations, and conventional and gene therapies.Pediatric discovery · 2023Article
- Gene therapy and genome editing for type I glycogen storage diseases.Frontiers in molecular medicine · 2023Review
- A glycogen storage disease type 1a patient with type 2 diabetes.BMC medical genomics · 2022Article
- Glycogen Storage Disease Type Ia Screening Using Dried Blood Spots on Filter Paper: Application of COP-PCR for Detection of the c.648G>T G6PC Gene Mutation.The Kobe journal of medical sciences · 2021Article
- Modeling Phenotypic Heterogeneity of Glycogen Storage Disease Type 1a Liver Disease in Mice by Somatic CRISPR/CRISPR-associated protein 9-Mediated Gene Editing.Hepatology (Baltimore, Md.) · 2021Article
- mRNA therapy restores euglycemia and prevents liver tumors in murine model of glycogen storage disease.Nature communications · 2021Article
- Correction of metabolic abnormalities in a mouse model of glycogen storage disease type Ia by CRISPR/Cas9-based gene editing.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
unlabelledGlycogen storage disease type Ia (GSD-Ia), which is characterized by impaired glucose homeostasis and chronic risk of hepatocellular adenoma (HCA), is caused by deficiencies in the endoplasmic reticulum (ER)-associated glucose-6-phosphatase-α (G6Pase-α or G6PC) that hydrolyzes glucose-6-phosphate (G6P) to glucose. G6Pase-α activity depends on the G6P transporter (G6PT) that translocates G6P from the cytoplasm into the ER lumen. The functional coupling of G6Pase-α and G6PT maintains interprandial glucose homeostasis. We have shown previously that gene therapy mediated by AAV-GPE, an adeno-associated virus (AAV) vector expressing G6Pase-α directed by the human G6PC promoter/enhancer (GPE), completely normalizes hepatic G6Pase-α deficiency in GSD-Ia (G6pc(-/-) ) mice for at least 24 weeks. However, a recent study showed that within 78 weeks of gene deletion, all mice lacking G6Pase-α in the liver develop HCA. We now show that gene therapy mediated by AAV-GPE maintains efficacy for at least 70-90 weeks for mice expressing more than 3% of wild-type hepatic G6Pase-α activity. The treated mice displayed normal hepatic fat storage, had normal blood metabolite and glucose tolerance profiles, had reduced fasting blood insulin levels, maintained normoglycemia over a 24-hour fast, and had no evidence of hepatic abnormalities. After a 24-hour fast, hepatic G6PT messenger RNA levels in G6pc(-/-) mice receiving gene therapy were markedly increased. Because G6PT transport is the rate-limiting step in microsomal G6P metabolism, this may explain why the treated G6pc(-/-) mice could sustain prolonged fasts. The low fasting blood insulin levels and lack of hepatic steatosis may explain the absence of HCA.
conclusionThese results confirm that AAV-GPE-mediated gene transfer corrects hepatic G6Pase-α deficiency in murine GSD-Ia and prevents chronic HCA formation.
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