ArticleThe Journal of clinical investigation2009
Dystrophins carrying spectrin-like repeats 16 and 17 anchor nNOS to the sarcolemma and enhance exercise performance in a mouse model of muscular dystrophy.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06290713 (Vasodilators and Exercise as Adjuvant Therapy for Duchenne Muscular Dystrophy), which is not on this map. Cited by 232 papers, 2 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.
Vasodilators and Exercise as Adjuvant Therapy for Duchenne Muscular Dystrophy (VASO-REx Study)
Who cites it
232 citing papers in PubMed, 2 syntheses or guidelines pooled it, 378 citations in OpenAlex.
- Muscle and cardiac therapeutic strategies for Duchenne muscular dystrophy: past, present, and future.Pharmacological reports : PR · 2020Pooled it
- WHOLE-BODY VIBRATION EXERCISE IS WELL TOLERATED IN PATIENTS WITH DUCHENNE MUSCULAR DYSTROPHY: A SYSTEMATIC REVIEW.African journal of traditional, complementary, and alternative medicines : AJTCAM · 2017Pooled it
- A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy.Neurology · 2017Trial
- Sodium nitrate alleviates functional muscle ischaemia in patients with Becker muscular dystrophy.The Journal of physiology · 2015Trial
- Combined isosorbide dinitrate and ibuprofen as a novel therapy for muscular dystrophies: evidence from Phase I studies in healthy volunteers.Drug design, development and therapy · 2014Trial
- Tadalafil alleviates muscle ischemia in patients with Becker muscular dystrophy.Science translational medicine · 2012Trial
- Myovascular Niche: The Role of Endothelial Cells in Skeletal Muscle Health and Disease.Circulation research · 2026Review
- AAVcc47-The Yale journal of biology and medicine · 2026Article
- Dystrophin-gene mutation location influences severity of electroretinogram defects in mouse models of Duchenne muscular dystrophy.BMC medicine · 2026Article
- Viscoelastic properties of dystrophin-deficient mouse skeletal muscles are resilient to isometric fatiguing exercise.Physiological reports · 2026Article
- Histone deacetylases in Duchenne muscular dystrophy: a role in the mechanism of disease and a target for inhibition.Clinical epigenetics · 2025Review
- Conditional Dmd ablation in muscle and brain causes profound effects on muscle function and neurobehavior.Communications biology · 2025Article
- AAV microdystrophin gene replacement therapy for Duchenne muscular dystrophy: progress and prospects.Gene therapy · 2025Review
- Enhanced therapeutic potential of a microdystrophin with an extended C-terminal domain.Molecular therapy. Methods & clinical development · 2025Article
- Expression of full-length dystrophin reverses muscular dystrophy defects in young and old mdx4cv mice.The Journal of clinical investigation · 2025Article
- The road toward AAV-mediated gene therapy of Duchenne muscular dystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Skeletal muscle disorders as risk factors for type 2 diabetes.Molecular and cellular endocrinology · 2025Review
- Extracellular matrix: Dystroglycan interactions-Roles for the dystrophin-associated glycoprotein complex in skeletal tissue dynamics.International journal of experimental pathology · 2025Review
- Adeno-Associated Virus 8 and 9 Myofibre Type/Size Tropism Profiling Reveals Therapeutic Effect of Microdystrophin in Canines.Journal of cachexia, sarcopenia and muscle · 2025Article
- Epigenetic control of myogenic identity of human muscle stem cells in Duchenne muscular dystrophy.iScience · 2024Article
172 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Sarcolemma-associated neuronal NOS (nNOS) plays a critical role in normal muscle physiology. In Duchenne muscular dystrophy (DMD), the loss of sarcolemmal nNOS leads to functional ischemia and muscle damage; however, the mechanism of nNOS subcellular localization remains incompletely understood. According to the prevailing model, nNOS is recruited to the sarcolemma by syntrophin, and in DMD this localization is altered. Intriguingly, the presence of syntrophin on the membrane does not always restore sarcolemmal nNOS. Thus, we wished to determine whether dystrophin functions in subcellular localization of nNOS and which regions may be necessary. Using in vivo transfection of dystrophin deletion constructs, we show that sarcolemmal targeting of nNOS was dependent on the spectrin-like repeats 16 and 17 (R16/17) within the rod domain. Treatment of mdx mice (a DMD model) with R16/17-containing synthetic dystrophin genes effectively ameliorated histological muscle pathology and improved muscle strength as well as exercise performance. Furthermore, sarcolemma-targeted nNOS attenuated alpha-adrenergic vasoconstriction in contracting muscle and improved muscle perfusion during exercise as measured by Doppler and microsphere circulation. In summary, we have identified the dystrophin spectrin-like repeats 16 and 17 as a novel scaffold for nNOS sarcolemmal targeting. These data suggest that muscular dystrophy gene therapies based on R16/17-containing dystrophins may yield better clinical outcomes than the current therapies.
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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.