ArticleHuman molecular genetics2014
Partial restoration of cardiac function with ΔPDZ nNOS in aged mdx model of Duchenne cardiomyopathy.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Muscle and cardiac therapeutic strategies for Duchenne muscular dystrophy: past, present, and future.Pharmacological reports : PR · 2020Pooled it
- Sildenafil does not improve cardiomyopathy in Duchenne/Becker muscular dystrophy.Annals of neurology · 2014Trial
- Lipin1 restores nNOS sarcolemmal localization and improves fatigue resistance in Duchenne muscular dystrophy.American journal of physiology. Cell physiology · 2026Article
- Transcriptional changes of genes encoding sarcoplasmic reticulum calcium binding and up-taking proteins in normal and Duchenne muscular dystrophy dogs.BMC musculoskeletal disorders · 2024Article
- Cardiac CIP protein regulates dystrophic cardiomyopathy.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Dystrophin deficiency impairs vascular structure and function in the canine model of Duchenne muscular dystrophy.The Journal of pathology · 2021Article
- Microutrophin expression in dystrophic mice displays myofiber type differences in therapeutic effects.PLoS genetics · 2020Article
- Multi-Compartment, Early Disruption of cGMP and cAMP Signalling in Cardiac Myocytes from theInternational journal of molecular sciences · 2020Article
- Single SERCA2a Therapy Ameliorated Dilated Cardiomyopathy for 18 Months in a Mouse Model of Duchenne Muscular Dystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Antagonism of the Thromboxane-Prostanoid Receptor as a Potential Therapy for Cardiomyopathy of Muscular Dystrophy.Journal of the American Heart Association · 2019Article
- Cardiac Pathophysiology and the Future of Cardiac Therapies in Duchenne Muscular Dystrophy.International journal of molecular sciences · 2019Review
- Dystrophin R16/17 protein therapy restores sarcolemmal nNOS in trans and improves muscle perfusion and function.Molecular medicine (Cambridge, Mass.) · 2019Article
- Targeting angiogenesis in Duchenne muscular dystrophy.Cellular and molecular life sciences : CMLS · 2019Review
- Dystrophin R16/17-syntrophin PDZ fusion protein restores sarcolemmal nNOSμ.Skeletal muscle · 2018Article
- Cardiac-Specific Expression of ΔH2-R15 Mini-Dystrophin Normalized All Electrocardiogram Abnormalities and the End-Diastolic Volume in a 23-Month-Old Mouse Model of Duchenne Dilated Cardiomyopathy.Human gene therapy · 2018Article
- Nanotherapy for Duchenne muscular dystrophy.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2018Review
- Dystrophic Cardiomyopathy-Potential Role of Calcium in Pathogenesis, Treatment and Novel Therapies.Genes · 2017Review
- Uniform low-level dystrophin expression in the heart partially preserved cardiac function in an aged mouse model of Duchenne cardiomyopathy.Journal of molecular and cellular cardiology · 2017Article
- Dystrophin contains multiple independent membrane-binding domains.Human molecular genetics · 2016Article
- Viral vector-mediated gene therapies.Current opinion in neurology · 2015Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Transgenic gene deletion/over-expression studies have established the cardioprotective role of neuronal nitric oxide synthase (nNOS). However, it remains unclear whether nNOS-mediated heart protection can be translated to gene therapy. In this study, we generated an adeno-associated virus (AAV) nNOS vector and tested its therapeutic efficacy in the aged mdx model of Duchenne cardiomyopathy. A PDZ domain-deleted nNOS gene (ΔPDZ nNOS) was packaged into tyrosine mutant AAV-9 and delivered to the heart of ~14-month-old female mdx mice, a phenotypic model of Duchenne cardiomyopathy. Seven months later, we observed robust nNOS expression in the myocardium. Supra-physiological ΔPDZ nNOS expression significantly reduced myocardial fibrosis, inflammation and apoptosis. Importantly, electrocardiography and left ventricular hemodynamics were significantly improved in treated mice. Additional studies revealed increased phosphorylation of phospholamban and p70S6K. Collectively, we have demonstrated the therapeutic efficacy of the AAV ΔPDZ nNOS vector in a symptomatic Duchenne cardiomyopathy model. Our results suggest that the cardioprotective role of ΔPDZ nNOS is likely through reduced apoptosis, enhanced phospholamban phosphorylation and improved Akt/mTOR/p70S6K signaling. Our study has opened the door to treat Duchenne cardiomyopathy with ΔPDZ nNOS gene transfer.
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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.