ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018
Inhibition of Glycogen Synthase II with RNAi Prevents Liver Injury in Mouse Models of Glycogen Storage Diseases.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Chronic thermal stress affects growth, liver morphology and molecular responses but allows recovery at optimal temperature in juvenile zebrafish (Danio rerio).Journal of fish biology · 2026Article
- RNA-Based Therapies for Inherited Metabolic Disorders.Journal of inherited metabolic disease · 2026Review
- Enhanced lysosomal glycogen breakdown is associated with liver tumorigenesis in glycogen storage disease type III.JHEP reports : innovation in hepatology · 2026Article
- Cardiovascular involvement in glycogen storage diseases.Nature reviews. Cardiology · 2026Review
- Synergism of dual AAV gene therapy and rapamycin rescues GSDIII phenotype in muscle and liver.JCI insight · 2024Article
- Gene therapy for glycogen storage diseases.Journal of inherited metabolic disease · 2024Review
- Pathological modeling of glycogen storage disease type III with CRISPR/Cas9 edited human pluripotent stem cells.Frontiers in cell and developmental biology · 2023Article
- Crosstalk between Glycogen-Selective Autophagy, Autophagy and Apoptosis as a Road towards Modifier Gene Discovery and New Therapeutic Strategies for Glycogen Storage Diseases.Life (Basel, Switzerland) · 2022Review
- Vasorin Deletion in C57BL/6J Mice Induces Hepatocyte Autophagy through Glycogen-Mediated mTOR Regulation.Nutrients · 2022Article
- Novel Gene-Correction-Based Therapeutic Modalities for Monogenic Liver Disorders.Bioengineering (Basel, Switzerland) · 2022Review
- Mechanism of glycogen synthase inactivation and interaction with glycogenin.Nature communications · 2022Article
- High Starch in Diet Leads to Disruption of Hepatic Glycogen Metabolism and Liver Fibrosis in Largemouth Bass (Frontiers in physiology · 2022Article
- The potential of dietary treatment in patients with glycogen storage disease type IV.Journal of inherited metabolic disease · 2021Observational
- 251st ENMC international workshop: Polyglucosan storage myopathies 13-15 December 2019, Hoofddorp, the Netherlands.Neuromuscular disorders : NMD · 2021Article
- Ovariectomy Impaired Hepatic Glucose and Lipid Homeostasis and Altered the Gut Microbiota in Mice With Different Diets.Frontiers in endocrinology · 2021Article
- Preclinical Research in Glycogen Storage Diseases: A Comprehensive Review of Current Animal Models.International journal of molecular sciences · 2020Review
- A Novel Gene Therapy Approach for GSD III Using an AAV Vector Encoding a Bacterial Glycogen Debranching Enzyme.Molecular therapy. Methods & clinical development · 2020Article
- Delivery of Oligonucleotides to the Liver with GalNAc: From Research to Registered Therapeutic Drug.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Review
- Discovery and Development of Small-Molecule Inhibitors of Glycogen Synthase.Journal of medicinal chemistry · 2020Article
- Gene therapy for glycogen storage diseases.Human molecular genetics · 2019Review
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glycogen storage diseases (GSDs) of the liver are devastating disorders presenting with fasting hypoglycemia as well as hepatic glycogen and lipid accumulation, which could lead to long-term liver damage. Diet control is frequently utilized to manage the potentially dangerous hypoglycemia, but there is currently no effective pharmacological treatment for preventing hepatomegaly and concurrent liver metabolic abnormalities, which could lead to fibrosis, cirrhosis, and hepatocellular adenoma or carcinoma. In this study, we demonstrate that inhibition of glycogen synthesis using an RNAi approach to silence hepatic Gys2 expression effectively prevents glycogen synthesis, glycogen accumulation, hepatomegaly, fibrosis, and nodule development in a mouse model of GSD III. Mechanistically, reduction of accumulated abnormally structured glycogen prevents proliferation of hepatocytes and activation of myofibroblasts as well as infiltration of mononuclear cells. Additionally, we show that silencing Gys2 expression reduces hepatic steatosis in a mouse model of GSD type Ia, where we hypothesize that the reduction of glycogen also reduces the production of excess glucose-6-phosphate and its subsequent diversion to lipid synthesis. Our results support therapeutic silencing of GYS2 expression to prevent glycogen and lipid accumulation, which mediate initial signals that subsequently trigger cascades of long-term liver injury in GSDs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.