Trial reportLancet (London, England)2011
Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study.
Trial report in Lancet (London, England), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 474 papers, 5 of them syntheses 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.
Clinical Study to Assess the Safety fo AVI-4658 in Subjects With Duchenne Muscular Dystrophy Due to a Frame-shift Mutation Amenable to Correction by Skipping Exon 51.
Efficacy of Umbilical Cord Mesenchymal Stem Cells in Duchenne Muscular Dystrophy: Phase 1/2 Study
Who cites it
474 citing papers in PubMed, 5 syntheses or guidelines pooled it, 855 citations in OpenAlex.
- The presymptomatic phase of amyotrophic lateral sclerosis: are we merely scratching the surface?Journal of neurology · 2021Pooled it
- Alternative splicing and cancer: a systematic review.Signal transduction and targeted therapy · 2021Pooled it
- Muscle and cardiac therapeutic strategies for Duchenne muscular dystrophy: past, present, and future.Pharmacological reports : PR · 2020Pooled it
- RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges.Pharmacological reviews · 2020Pooled it
- Restorative treatments of dystrophin expression in Duchenne muscular dystrophy: A systematic review.Annals of clinical and translational neurology · 2020Pooled it
- Phase 1/2 trial of brogidirsen: Dual-targeting antisense oligonucleotides for exon 44 skipping in Duchenne muscular dystrophy.Cell reports. Medicine · 2025Trial
- Trial
- Open-Label Evaluation of Eteplirsen in Patients with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping: PROMOVI Trial.Journal of neuromuscular diseases · 2021Trial
- Resveratrol improves motor function in patients with muscular dystrophies: an open-label, single-arm, phase IIa study.Scientific reports · 2020Trial
- Assessment of Systemic Delivery of rAAVrh74.MHCK7.micro-dystrophin in Children With Duchenne Muscular Dystrophy: A Nonrandomized Controlled Trial.JAMA neurology · 2020Trial
- Increased dystrophin production with golodirsen in patients with Duchenne muscular dystrophy.Neurology · 2020Trial
- Trial
- FDA-approved antisense oligonucleotide therapies for duchenne muscular dystrophy: current status and future outlook.RNA biology · 2026Review
- Article
- Developing Metal-Polyphenol Network-Based Single-Protein Particle Encapsulation System for Sustained Release of Whey Protein to Mitigate Sarcopenia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Meta-analysis of adverse events in clinical studies with antisense oligonucleotide therapies.Molecular therapy. Nucleic acids · 2026Review
- SpliceSelectNet: a hierarchical Transformer-based deep learning model for splice site prediction.Nucleic acids research · 2026Article
- The Versatile Applications of Antisense Oligonucleotides in Modern Medicine.International journal of molecular sciences · 2026Review
- Expanding the toolbox: Emerging antisense oligonucleotide mechanisms for modulating gene expression.Molecular therapy. Nucleic acids · 2026Review
- Current and Emerging Therapeutic Strategies for the Treatment of Duchenne Muscular Dystrophy.Genes · 2026Review
414 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 8 institutions in 3 countries.
Funding
Abstract
backgroundWe report clinical safety and biochemical efficacy from a dose-ranging study of intravenously administered AVI-4658 phosphorodiamidate morpholino oligomer (PMO) in patients with Duchenne muscular dystrophy.
methodWe undertook an open-label, phase 2, dose-escalation study (0·5, 1·0, 2·0, 4·0, 10·0, and 20·0 mg/kg bodyweight) in ambulant patients with Duchenne muscular dystrophy aged 5-15 years with amenable deletions in DMD. Participants had a muscle biopsy before starting treatment and after 12 weekly intravenous infusions of AVI-4658. The primary study objective was to assess safety and tolerability of AVI-4658. The secondary objectives were pharmacokinetic properties and the ability of AVI-4658 to induce exon 51 skipping and dystrophin restoration by RT-PCR, immunohistochemistry, and immunoblotting. The study is registered, number NCT00844597.
findings19 patients took part in the study. AVI-4658 was well tolerated with no drug-related serious adverse events. AVI-4658 induced exon 51 skipping in all cohorts and new dystrophin protein expression in a significant dose-dependent (p=0·0203), but variable, manner in boys from cohort 3 (dose 2 mg/kg) onwards. Seven patients responded to treatment, in whom mean dystrophin fluorescence intensity increased from 8·9% (95% CI 7·1-10·6) to 16·4% (10·8-22·0) of normal control after treatment (p=0·0287). The three patients with the greatest responses to treatment had 21%, 15%, and 55% dystrophin-positive fibres after treatment and these findings were confirmed with western blot, which showed an increase after treatment of protein levels from 2% to 18%, from 0·9% to 17%, and from 0% to 7·7% of normal muscle, respectively. The dystrophin-associated proteins α-sarcoglycan and neuronal nitric oxide synthase were also restored at the sarcolemma. Analysis of the inflammatory infiltrate indicated a reduction of cytotoxic T cells in the post-treatment muscle biopsies in the two high-dose cohorts.
interpretationThe safety and biochemical efficacy that we present show the potential of AVI-4658 to become a disease-modifying drug for Duchenne muscular dystrophy.
fundingUK Medical Research Council; AVI BioPharma.
Indexed as
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.