ArticleMolecular therapy. Nucleic acids2014
Antisense Oligonucleotide-mediated Suppression of Muscle Glycogen Synthase 1 Synthesis as an Approach for Substrate Reduction Therapy of Pompe Disease.
Article in Molecular therapy. Nucleic acids, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Systematic Review of Genetic Substrate Reduction Therapy in Lysosomal Storage Diseases: Opportunities, Challenges and Delivery Systems.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Pooled it
- A Comprehensive Update on Pompe Disease: From Existing Therapies to Emerging Curative Strategies.International journal of molecular sciences · 2026Review
- Review
- Cardiovascular involvement in glycogen storage diseases.Nature reviews. Cardiology · 2026Review
- New advances in treating late-onset Pompe Disease: A narrative review.European journal of pediatrics · 2025Review
- Skeletal muscle effects of antisense oligonucleotides targeting glycogen synthase 1 in a mouse model of Pompe disease.Clinical and translational medicine · 2025Article
- Expansion of Splice-Switching Therapy with Antisense Oligonucleotides.International journal of molecular sciences · 2025Review
- Management of Pompe disease alongside and beyond ERT: a narrative review.Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2025Review
- Advances in Pompe Disease Treatment: From Enzyme Replacement to Gene Therapy.Molecular diagnosis & therapy · 2024Review
- Splice-Modulating Antisense Oligonucleotides as Therapeutics for Inherited Metabolic Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- Advances in functional lipid nanoparticles: from drug delivery platforms to clinical applications.3 Biotech · 2024Review
- Small-molecule inhibition of glycogen synthase 1 for the treatment of Pompe disease and other glycogen storage disorders.Science translational medicine · 2024Article
- A Comprehensive Update on Late-Onset Pompe Disease.Biomolecules · 2023Review
- Pompe Disease: a Clinical, Diagnostic, and Therapeutic Overview.Current treatment options in neurology · 2022Article
- Molecular basis for the regulation of human glycogen synthase by phosphorylation and glucose-6-phosphate.Nature structural & molecular biology · 2022Article
- Article
- Therapeutic Strategies For Tay-Sachs Disease.Frontiers in pharmacology · 2022Review
- Pharmacological Chaperone Therapy for Pompe Disease.Molecules (Basel, Switzerland) · 2021Review
- 251st ENMC international workshop: Polyglucosan storage myopathies 13-15 December 2019, Hoofddorp, the Netherlands.Neuromuscular disorders : NMD · 2021Article
- Case Report: Anesthetic Management and Electrical Cardiometry as Intensive Hemodynamic Monitoring During Cheiloplasty in an Infant With Enzyme-Replaced Pompe Disease and Preserved Preoperative Cardiac Function.Frontiers in pediatrics · 2021Article
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pompe disease is an autosomal recessive disorder caused by a deficiency of acid α-glucosidase (GAA; EC 3.2.1.20) and the resultant progressive lysosomal accumulation of glycogen in skeletal and cardiac muscles. Enzyme replacement therapy using recombinant human GAA (rhGAA) has proven beneficial in addressing several aspects of the disease such as cardiomyopathy and aberrant motor function. However, residual muscle weakness, hearing loss, and the risks of arrhythmias and osteopenia persist despite enzyme therapy. Here, we evaluated the relative merits of substrate reduction therapy (by inhibiting glycogen synthesis) as a potential adjuvant strategy. A phosphorodiamidate morpholino oligonucleotide (PMO) designed to invoke exon skipping and premature stop codon usage in the transcript for muscle specific glycogen synthase (Gys1) was identified and conjugated to a cell penetrating peptide (GS-PPMO) to facilitate PMO delivery to muscle. GS-PPMO systemic administration to Pompe mice led to a dose-dependent decrease in glycogen synthase transcripts in the quadriceps, and the diaphragm but not the liver. An mRNA response in the heart was seen only at the higher dose tested. Associated with these decreases in transcript levels were correspondingly lower tissue levels of muscle specific glycogen synthase and activity. Importantly, these reductions resulted in significant decreases in the aberrant accumulation of lysosomal glycogen in the quadriceps, diaphragm, and heart of Pompe mice. Treatment was without any overt toxicity, supporting the notion that substrate reduction by GS-PPMO-mediated inhibition of muscle specific glycogen synthase represents a viable therapeutic strategy for Pompe disease after further development.
Identifiers
What OpenQuestion holds
Registered trials
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.