Trial reportScience translational medicine2012
Tadalafil alleviates muscle ischemia in patients with Becker muscular dystrophy.
Trial report in Science translational medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 52 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Sodium Nitrate to Improve Blood Flow
Vasodilators and Exercise as Adjuvant Therapy for Duchenne Muscular Dystrophy (VASO-REx Study)
Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.
- Guideline
- A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy.Neurology · 2017Trial
- Effects of Sildenafil on Cerebrovascular Reactivity in Patients with Becker Muscular Dystrophy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2017Trial
- Sodium nitrate alleviates functional muscle ischaemia in patients with Becker muscular dystrophy.The Journal of physiology · 2015Trial
- Sildenafil does not improve cardiomyopathy in Duchenne/Becker muscular dystrophy.Annals of neurology · 2014Trial
- Sildenafil increases muscle protein synthesis and reduces muscle fatigue.Clinical and translational science · 2013Trial
- Assessing the therapeutic potential of PDE-5 inhibitors in adults: Insights from a multi-omics study.Physiological reports · 2026Article
- Mexico's First Heart Transplant in a Patient with Becker Muscular Dystrophy Reveals an Overlooked Cause of Idiopathic Dilated Cardiomyopathy.Muscles (Basel, Switzerland) · 2026Article
- Enhanced therapeutic potential of a microdystrophin with an extended C-terminal domain.Molecular therapy. Methods & clinical development · 2025Article
- Ubiquitination-targeted therapies improve BMD iPSC myogenic cell engraftment and dystrophin expressionMolecular therapy. Methods & clinical development · 2025Article
- Male mice treated with combined anti-fibrotic therapeutics, IPW5371 and tadalafil, are predisposed to adverse cardiovascular events.Frontiers in pharmacology · 2025Article
- A split-label design for simultaneous measurements of perfusion in distant slices by pulsed arterial spin labeling.Magnetic resonance in medicine · 2021Article
- The use of umbilical cord-derived mesenchymal stem cells in patients with muscular dystrophies: Results from compassionate use in real-life settings.Stem cells translational medicine · 2021Article
- Assessing the Use of the sGC Stimulator BAY-747, as a Potential Treatment for Duchenne Muscular Dystrophy.International journal of molecular sciences · 2021Article
- Intramuscular blood flow in Duchenne and Becker Muscular Dystrophy: Quantitative power Doppler sonography relates to disease severity.Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology · 2020Article
- Inhibition of FLT1 ameliorates muscular dystrophy phenotype by increased vasculature in a mouse model of Duchenne muscular dystrophy.PLoS genetics · 2019Article
- Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond.Nature reviews. Drug discovery · 2019Review
- 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
- Therapeutic developments for Duchenne muscular dystrophy.Nature reviews. Neurology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Becker muscular dystrophy (BMD) is a progressive X-linked muscle wasting disease for which there is no treatment. Like Duchenne muscular dystrophy (DMD), BMD is caused by mutations in the gene encoding dystrophin, a structural cytoskeletal protein that also targets other proteins to the muscle sarcolemma. Among these is neuronal nitric oxide synthase (nNOSμ), which requires certain spectrin-like repeats in dystrophin's rod domain and the adaptor protein α-syntrophin to be targeted to the sarcolemma. When healthy skeletal muscle is subjected to exercise, sarcolemmal nNOSμ-derived NO attenuates local α-adrenergic vasoconstriction, thereby optimizing perfusion of muscle. We found previously that this protective mechanism is defective-causing functional muscle ischemia-in dystrophin-deficient muscles of the mdx mouse (a model of DMD) and of children with DMD, in whom nNOSμ is mislocalized to the cytosol instead of the sarcolemma. We report that this protective mechanism also is defective in men with BMD in whom the most common dystrophin mutations disrupt sarcolemmal targeting of nNOSμ. In these men, the vasoconstrictor response, measured as a decrease in muscle oxygenation, to reflex sympathetic activation is not appropriately attenuated during exercise of the dystrophic muscles. In a randomized placebo-controlled crossover trial, we show that functional muscle ischemia is alleviated and normal blood flow regulation is fully restored in the muscles of men with BMD by boosting NO-cGMP (guanosine 3',5'-monophosphate) signaling with a single dose of the drug tadalafil, a phosphodiesterase 5A inhibitor. These results further support an essential role for sarcolemmal nNOSμ in the normal modulation of sympathetic vasoconstriction in exercising human skeletal muscle and implicate the NO-cGMP pathway as a putative new target for treating BMD.
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Identifiers
What OpenQuestion holds
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.