ArticleMolecular therapy : the journal of the American Society of Gene Therapy2014
Forelimb treatment in a large cohort of dystrophic dogs supports delivery of a recombinant AAV for exon skipping in Duchenne patients.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 114 citations in OpenAlex.
- Using MRI to quantify skeletal muscle pathology in Duchenne muscular dystrophy: A systematic mapping review.Muscle & nerve · 2021Pooled it
- Upper limb disease evolution in exon 53 skipping eligible patients with Duchenne muscular dystrophy.Annals of clinical and translational neurology · 2021Trial
- Longitudinal functional and NMR assessment of upper limbs in Duchenne muscular dystrophy.Neurology · 2016Trial
- Preclinical study of an optimized AAV cancer vaccine in a spontaneous canine model of oral melanoma.Molecular therapy. Oncology · 2026Article
- Canine Model of Duchenne Muscular Dystrophy.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Delivery of genetic medicines for muscular dystrophies.Cell reports. Medicine · 2025Review
- Comprehensive quantitative magnetic resonance imaging assessment of skeletal muscle pathophysiology in golden retriever muscular dystrophy: Insights from multicomponent water T2 and extracellular volume fraction.NMR in biomedicine · 2025Article
- Article
- Comprehensive Evaluation of Lipid Nanoparticles and Polyplex Nanomicelles for Muscle-Targeted mRNA Delivery.Pharmaceutics · 2023Article
- Systemic deletion ofProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Transcriptomic Analysis Reveals the Inability of Recombinant AAV8 to Activate Human Monocyte-Derived Dendritic Cells.International journal of molecular sciences · 2023Article
- Multiplexing AAV Serotype-Specific Neutralizing Antibodies in Preclinical Animal Models and Humans.Biomedicines · 2023Article
- Dystrophin and mini-dystrophin quantification by mass spectrometry in skeletal muscle for gene therapy development in Duchenne muscular dystrophy.Gene therapy · 2022Article
- Muscle regeneration affects Adeno Associated Virus 1 mediated transgene transcription.Scientific reports · 2022Article
- Therapeutic efficacy of new botulinum toxin identified in CCUG 7968 strain.Applied microbiology and biotechnology · 2021Article
- AAV8 locoregional delivery induces long-term expression of an immunogenic transgene in macaques despite persisting local inflammation.Molecular therapy. Methods & clinical development · 2021Article
- Article
- Current Genetic Survey and Potential Gene-Targeting Therapeutics for Neuromuscular Diseases.International journal of molecular sciences · 2020Review
- Of rAAV and Men: From Genetic Neuromuscular Disorder Efficacy and Toxicity Preclinical Studies to Clinical Trials and Back.Journal of personalized medicine · 2020Review
- Myostatin Is a Quantifiable Biomarker for Monitoring Pharmaco-gene Therapy in Duchenne Muscular Dystrophy.Molecular therapy. Methods & clinical development · 2020Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
44 authors at 9 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disorder caused by mutations in the dystrophin gene, without curative treatment yet available. Our study provides, for the first time, the overall safety profile and therapeutic dose of a recombinant adeno-associated virus vector, serotype 8 (rAAV8) carrying a modified U7snRNA sequence promoting exon skipping to restore a functional in-frame dystrophin transcript, and injected by locoregional transvenous perfusion of the forelimb. Eighteen Golden Retriever Muscular Dystrophy (GRMD) dogs were exposed to increasing doses of GMP-manufactured vector. Treatment was well tolerated in all, and no acute nor delayed adverse effect, including systemic and immune toxicity was detected. There was a dose relationship for the amount of exon skipping with up to 80% of myofibers expressing dystrophin at the highest dose. Similarly, histological, nuclear magnetic resonance pathological indices and strength improvement responded in a dose-dependent manner. The systematic comparison of effects using different independent methods, allowed to define a minimum threshold of dystrophin expressing fibers (>33% for structural measures and >40% for strength) under which there was no clear-cut therapeutic effect. Altogether, these results support the concept of a phase 1/2 trial of locoregional delivery into upper limbs of nonambulatory DMD patients.
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