ArticleMolecular medicine (Cambridge, Mass.)2019
Dystrophin R16/17 protein therapy restores sarcolemmal nNOS in trans and improves muscle perfusion and function.
Article in Molecular medicine (Cambridge, Mass.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Lipin1 restores nNOS sarcolemmal localization and improves fatigue resistance in Duchenne muscular dystrophy.American journal of physiology. Cell physiology · 2026Article
- Myovascular Niche: The Role of Endothelial Cells in Skeletal Muscle Health and Disease.Circulation research · 2026Review
- Sensitivity of Different Clinical Outcome Measures in Assessing Adults With Becker Muscular Dystrophy: A 3-Year Natural History Study.Neurology · 2025Article
- Scientific and Technological Prospecting on Polymeric Particles Containing Extracellular Matrix Peptides for the Treatment of Duchenne Muscular Dystrophy.Recent advances in drug delivery and formulation · 2025Review
- The Role of Gene Expression Dysregulation in the Pathogenesis of Mucopolysaccharidosis: A Comparative Analysis of Shared and Specific Molecular Markers in Neuronopathic and Non-Neuronopathic Types of the Disease.International journal of molecular sciences · 2024Article
- 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
- Dystrophin- and Utrophin-Based Therapeutic Approaches for Treatment of Duchenne Muscular Dystrophy: A Comparative Review.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- Sub-region analysis of DMD gene in cases with idiopathic generalized epilepsy.Neurogenetics · 2023Article
- The X-linked Becker muscular dystrophy (bmx) mouse models Becker muscular dystrophy via deletion of murine dystrophin exons 45-47.Journal of cachexia, sarcopenia and muscle · 2023Article
- Pathophysiology and Management of Fatigue in Neuromuscular Diseases.International journal of molecular sciences · 2023Review
- Episodic Binge-like Ethanol Reduces Skeletal Muscle Strength Associated with Atrophy, Fibrosis, and Inflammation in Young Rats.International journal of molecular sciences · 2023Article
- CRISPR applications for Duchenne muscular dystrophy: From animal models to potential therapies.WIREs mechanisms of disease · 2023Review
- Promising therapeutic approaches of utrophin replacing dystrophin in the treatment of Duchenne muscular dystrophy.Fundamental research · 2022Review
- Nanomedicine for Treating Muscle Dystrophies: Opportunities, Challenges, and Future Perspectives.International journal of molecular sciences · 2022Review
- Transcriptome changes during the initiation and progression of Duchenne muscular dystrophy in Caenorhabditis elegans.Human molecular genetics · 2020Article
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Authors and funding
7 authors at 2 institutions in 1 country.
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Abstract
backgroundDelocalization of neuronal nitric oxide synthase (nNOS) from the sarcolemma leads to functional muscle ischemia. This contributes to the pathogenesis in cachexia, aging and muscular dystrophy. Mutations in the gene encoding dystrophin result in Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). In many BMD patients and DMD patients that have been converted to BMD by gene therapy, sarcolemmal nNOS is missing due to the lack of dystrophin nNOS-binding domain.
methodsDystrophin spectrin-like repeats 16 and 17 (R16/17) is the sarcolemmal nNOS localization domain. Here we explored whether R16/17 protein therapy can restore nNOS to the sarcolemma and prevent functional ischemia in transgenic mice which expressed an R16/17-deleted human micro-dystrophin gene in the dystrophic muscle. The palmitoylated R16/17.GFP fusion protein was conjugated to various cell-penetrating peptides and produced in the baculovirus-insect cell system. The best fusion protein was delivered to the transgenic mice and functional muscle ischemia was quantified.
resultsAmong five candidate cell-penetrating peptides, the mutant HIV trans-acting activator of transcription (TAT) protein transduction domain (mTAT) was the best in transferring the R16/17.GFP protein to the muscle. Systemic delivery of the mTAT.R16/17.GFP protein to micro-dystrophin transgenic mice successfully restored sarcolemmal nNOS without inducing T cell infiltration. More importantly, R16/17 protein therapy effectively prevented treadmill challenge-induced force loss and improved muscle perfusion during contraction.
conclusionsOur results suggest that R16/17 protein delivery is a highly promising therapy for muscle diseases involving sarcolemmal nNOS delocalizaton.
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