ArticleMolecular therapy. Nucleic acids2017
GAA Deficiency in Pompe Disease Is Alleviated by Exon Inclusion in iPSC-Derived Skeletal Muscle Cells.
Article in Molecular therapy. Nucleic acids, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 66 citations in OpenAlex.
- The ACE I/D polymorphism does not explain heterogeneity of natural course and response to enzyme replacement therapy in Pompe disease.PloS one · 2018Trial
- A Comprehensive Update on Pompe Disease: From Existing Therapies to Emerging Curative Strategies.International journal of molecular sciences · 2026Review
- Elucidating the role of human skeletal muscles in the pathogenesis of enterovirus D68 infection.Life science alliance · 2025Article
- Splicing correction by peptide-conjugated morpholinos as a novel treatment for late-onset Pompe disease.Molecular therapy. Nucleic acids · 2025Article
- Skeletal muscle effects of antisense oligonucleotides targeting glycogen synthase 1 in a mouse model of Pompe disease.Clinical and translational medicine · 2025Article
- 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
- Case Report: Incidental late-onset Pompe disease diagnosis in a man with no clinical and instrumental evidence of neuromuscular dysfunction.Frontiers in genetics · 2025Article
- Functional Analysis of Complex Structural and Splice-Altering Variants in theHuman mutation · 2025Article
- Splice-Modulating Antisense Oligonucleotides as Therapeutics for Inherited Metabolic Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- A knock down strategy for rapid, generic, and versatile modelling of muscular dystrophies in 3D-tissue-engineered-skeletal muscle.Skeletal muscle · 2024Article
- Light and Shadows in Newborn Screening for Lysosomal Storage Disorders: Eight Years of Experience in Northeast Italy.International journal of neonatal screening · 2023Article
- Highly contractile 3D tissue engineered skeletal muscles from human iPSCs reveal similarities with primary myoblast-derived tissues.Stem cell reports · 2023Article
- A Comprehensive Update on Late-Onset Pompe Disease.Biomolecules · 2023Review
- Generation of two induced pluripotent stem cell lines (CHOCi002-A and CHOCi003-A) from Pompe disease patients with compound heterozygous mutations in the GAA gene.Stem cell research · 2023Article
- Human iPSC-derived preclinical models to identify toxicity of tumor-specific T cells with clinical potential.Molecular therapy. Methods & clinical development · 2023Article
- Newborn screening for Pompe disease in Italy: Long-term results and future challenges.Molecular genetics and metabolism reports · 2022Article
- Lentiviral gene therapy prevents anti-human acid α-glucosidase antibody formation in murine Pompe disease.Molecular therapy. Methods & clinical development · 2022Article
- A balanced Oct4 interactome is crucial for maintaining pluripotency.Science advances · 2022Article
- Myotonic dystrophy type 1 embryonic stem cells show decreased myogenic potential, increased CpG methylation at the DMPK locus and RNA mis-splicing.Biology open · 2022Article
- Therapeutic Strategies For Tay-Sachs Disease.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pompe disease is a metabolic myopathy caused by deficiency of the acid α-glucosidase (GAA) enzyme and results in progressive wasting of skeletal muscle cells. The c.-32-13T>G (IVS1) GAA variant promotes exon 2 skipping during pre-mRNA splicing and is the most common variant for the childhood/adult disease form. We previously identified antisense oligonucleotides (AONs) that promoted GAA exon 2 inclusion in patient-derived fibroblasts. It was unknown how these AONs would affect GAA splicing in skeletal muscle cells. To test this, we expanded induced pluripotent stem cell (iPSC)-derived myogenic progenitors and differentiated these to multinucleated myotubes. AONs restored splicing in myotubes to a similar extent as in fibroblasts, suggesting that they act by modulating the action of shared splicing regulators. AONs targeted the putative polypyrimidine tract of a cryptic splice acceptor site that was part of a pseudo exon in GAA intron 1. Blocking of the cryptic splice donor of the pseudo exon with AONs likewise promoted GAA exon 2 inclusion. The simultaneous blocking of the cryptic acceptor and cryptic donor sites restored the majority of canonical splicing and alleviated GAA enzyme deficiency. These results highlight the relevance of cryptic splicing in human disease and its potential as therapeutic target for splicing modulation using AONs.
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