ArticleJournal of molecular and cellular cardiology2012
AAV micro-dystrophin gene therapy alleviates stress-induced cardiac death but not myocardial fibrosis in >21-m-old mdx mice, an end-stage model of Duchenne muscular dystrophy cardiomyopathy.
Article in Journal of molecular and cellular cardiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- A Decade of Progress in Gene Targeted Therapeutic Strategies in Duchenne Muscular Dystrophy: A Systematic Review.Frontiers in bioengineering and biotechnology · 2022Pooled it
- Genetic strategies for therapy of Duchenne muscular dystrophy.Molecular therapy. Nucleic acids · 2025Review
- AAV microdystrophin gene replacement therapy for Duchenne muscular dystrophy: progress and prospects.Gene therapy · 2025Review
- Review
- Long-Term Dystrophin Replacement Therapy in Duchenne Muscular Dystrophy Causes Cardiac Inflammation.JACC. Basic to translational science · 2025Article
- Advances in Duchenne Muscular Dystrophy: Diagnostic Techniques and Dystrophin Domain Insights.International journal of molecular sciences · 2025Review
- Review
- In Silico Structural Prediction for the Generation of Novel Performant Midi-Dystrophins Based on Intein-Mediated Dual AAV Approach.International journal of molecular sciences · 2024Article
- Article
- Systemic delivery of full-length dystrophin in Duchenne muscular dystrophy mice.Nature communications · 2024Article
- Inhibition of miR-25 ameliorates cardiac and skeletal muscle dysfunction in agedMolecular therapy. Nucleic acids · 2024Article
- Potential limitations of microdystrophin gene therapy for Duchenne muscular dystrophy.JCI insight · 2024Article
- The BALB/c.mdx62 mouse exhibits a dystrophic muscle pathology and is a model of Duchenne muscular dystrophy.Disease models & mechanisms · 2024Article
- Assessment of Therapeutic Potential of a Dual AAV Approach for Duchenne Muscular Dystrophy.International journal of molecular sciences · 2023Article
- Microdystrophin Expression as a Surrogate Endpoint for Duchenne Muscular Dystrophy Clinical Trials.Human gene therapy · 2023Article
- Lifelong Outcomes of Systemic Adeno-Associated Virus Micro-Dystrophin Gene Therapy in a Murine Duchenne Muscular Dystrophy Model.Human gene therapy · 2023Article
- Myostatin/Activin Receptor Ligands in Muscle and the Development Status of Attenuating Drugs.Endocrine reviews · 2022Review
- Therapeutic Application of Extracellular Vesicles-Capsulated Adeno-Associated Virus Vector viaInternational journal of molecular sciences · 2022Review
- Proteomic analysis identifies key differences in the cardiac interactomes of dystrophin and micro-dystrophin.Human molecular genetics · 2021Article
- Micro-dystrophin gene therapy prevents heart failure in an improved Duchenne muscular dystrophy cardiomyopathy mouse model.JCI insight · 2021Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Duchenne muscular dystrophy (DMD) is a fatal genetic disease caused by the absence of the sarcolemmal protein dystrophin. Dilated cardiomyopathy leading to heart failure is a significant source of morbidity and mortality in DMD. We recently demonstrated amelioration of DMD heart disease in 16 to 20-m-old dystrophin-null mdx mice using adeno-associated virus (AAV) mediated micro-dystrophin gene therapy. DMD patients show severe heart disease near the end of their life expectancy. Similarly, mdx mice exhibit profoundly worsening heart disease when they reach beyond 21 months of age. To more rigorously test micro-dystrophin therapy, we treated mdx mice that were between 21.2 and 22.7-m-old (average, 22.1 ± 0.2 months; N=8). The ∆R4-23/∆C micro-dystrophin gene was packaged in the cardiotropic AAV-9 virus. 5×10(12) viral genome particles/mouse were delivered to mdx mice via the tail vein. AAV transduction, myocardial fibrosis and heart function were examined 1.7 ± 0.2 months after gene therapy. Efficient micro-dystrophin expression was observed in the myocardium of treated mice. Despite the robust dystrophin expression, myocardial fibrosis was not mitigated. Most hemodynamic parameters were not improved either. However, ECG abnormalities were partially corrected. Importantly, treated mice became more resistant to dobutamine-induced cardiac death. In summary, we have revealed for the first time the potential benefits and limitations of AAV micro-dystrophin therapy in end-stage Duchenne dilated cardiomyopathy. Our findings have important implications for the use of AAV gene therapy in dilated cardiomyopathy and heart failure.
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