ArticleSkeletal muscle2015
Elusive sources of variability of dystrophin rescue by exon skipping.
Article in Skeletal muscle, 2015. 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, 32 citations in OpenAlex.
- Current and Emerging Therapeutic Strategies for the Treatment of Duchenne Muscular Dystrophy.Genes · 2026Review
- Systematic analysis of the adverse effects of used clinical antisense oligonucleotide drugs in DMD patients based on the FAERS database.European journal of clinical pharmacology · 2026Article
- A combinatorial oligonucleotide therapy to improve dystrophin restoration and dystrophin-deficient muscle health.Molecular therapy. Nucleic acids · 2025Article
- Deletion of miR-146a enhances therapeutic protein restoration in model of dystrophin exon skipping.Molecular therapy. Nucleic acids · 2024Article
- Comprehensive review of adverse reactions and toxicology in ASO-based therapies for Duchenne Muscular Dystrophy: From FDA-approved drugs to peptide-conjugated ASO.Current research in toxicology · 2024Article
- Exon 44 skipping in Duchenne muscular dystrophy: NS-089/NCNP-02, a dual-targeting antisense oligonucleotide.Molecular therapy. Nucleic acids · 2023Article
- Control of backbone chemistry and chirality boost oligonucleotide splice switching activity.Nucleic acids research · 2022Article
- MOTS-c promotes phosphorodiamidate morpholino oligomer uptake and efficacy in dystrophic mice.EMBO molecular medicine · 2021Article
- Interrogation of Dystrophin and Dystroglycan Complex Protein Turnover After Exon Skipping Therapy.Journal of neuromuscular diseases · 2021Article
- Morpholino-induced exon skipping stimulates cell-mediated and humoral responses to dystrophin in mdx mice.The Journal of pathology · 2019Article
- What is the level of dystrophin expression required for effective therapy of Duchenne muscular dystrophy?Journal of muscle research and cell motility · 2019Review
- Efficacy of Multi-exon Skipping Treatment in Duchenne Muscular Dystrophy Dog Model Neonates.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Multiple Exon Skipping in the Duchenne Muscular Dystrophy Hot Spots: Prospects and Challenges.Journal of personalized medicine · 2018Review
- The macrophage as a Trojan horse for antisense oligonucleotide delivery.Expert opinion on therapeutic targets · 2018Article
- Synthesis, Characterization, and Function of an RNA-Based Transfection Reagent.Current protocols in nucleic acid chemistry · 2018Article
- Myoblasts and macrophages are required for therapeutic morpholino antisense oligonucleotide delivery to dystrophic muscle.Nature communications · 2017Article
- Correction of the Exon 2 Duplication in DMD Myoblasts by a Single CRISPR/Cas9 System.Molecular therapy. Nucleic acids · 2017Article
- Mitochondria mediate cell membrane repair and contribute to Duchenne muscular dystrophy.Cell death and differentiation · 2017Article
- Functional improvement of dystrophic muscle by repression of utrophin: let-7c interaction.PloS one · 2017Article
- An amphipathicRSC advances · 2017Article
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Authors and funding
20 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundSystemic delivery of anti-sense oligonucleotides to Duchenne muscular dystrophy (DMD) patients to induce de novo dystrophin protein expression in muscle (exon skipping) is a promising therapy. Treatment with Phosphorodiamidate morpholino oligomers (PMO) lead to shorter de novo dystrophin protein in both animal models and DMD boys who otherwise lack dystrophin; however, restoration of dystrophin has been observed to be highly variable. Understanding the factors causing highly variable induction of dystrophin expression in pre-clinical models would likely lead to more effective means of exon skipping in both pre-clinical studies and human clinical trials.
methodsIn the present study, we investigated possible factors that might lead to the variable success of exon skipping using morpholino drugs in the mdx mouse model. We tested whether specific muscle groups or fiber types showed better success than others and also correlated residual PMO concentration in muscle with the amount of de novo dystrophin protein 1 month after a single high-dose morpholino injection (800 mg/kg). We compared the results from six muscle groups using three different methods of dystrophin quantification: immunostaining, immunoblotting, and mass spectrometry assays.
resultsThe triceps muscle showed the greatest degree of rescue (average 38±28 % by immunostaining). All three dystrophin detection methods were generally concordant for all muscles. We show that dystrophin rescue occurs in a sporadic patchy pattern with high geographic variability across muscle sections. We did not find a correlation between residual morpholino drug in muscle tissue and the degree of dystrophin expression.
conclusionsWhile we found some evidence of muscle group enhancement and successful rescue, our data also suggest that other yet-undefined factors may underlie the observed variability in the success of exon skipping. Our study highlights the challenges associated with quantifying dystrophin in clinical trials where a single small muscle biopsy is taken from a DMD patient.
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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.