ArticleJournal of the American Heart Association2016
Tadalafil Treatment Delays the Onset of Cardiomyopathy in Dystrophin-Deficient Hearts.
Article in Journal of the American Heart Association, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Muscle and cardiac therapeutic strategies for Duchenne muscular dystrophy: past, present, and future.Pharmacological reports : PR · 2020Pooled it
- Effect of Tadalafil on cardiac function and left ventricular dimensions in Duchenne muscular dystrophy: safety and cardiac MRI substudy results from a randomized, placebo-controlled trial.BMC cardiovascular disorders · 2025Trial
- A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy.Neurology · 2017Trial
- Combination S100A1 and ARC gene therapy as a treatment for Duchenne muscular dystrophy cardiomyopathy.JCI insight · 2026Article
- Systemic responses to intravenous rAAV administration in boys with Duchenne muscular dystrophy.Frontiers in molecular medicine · 2026Article
- Potential beneficial impacts of tadalafil on cardiovascular diseases.Journal of the Chinese Medical Association : JCMA · 2025Review
- Potential limitations of microdystrophin gene therapy for Duchenne muscular dystrophy.JCI insight · 2024Article
- Pharmacotherapeutic Approaches to Treatment of Muscular Dystrophies.Biomolecules · 2023Review
- Ion Channels of the Sarcolemma and Intracellular Organelles in Duchenne Muscular Dystrophy: A Role in the Dysregulation of Ion Homeostasis and a Possible Target for Therapy.International journal of molecular sciences · 2023Review
- Pharmacological TRPC6 inhibition improves survival and muscle function in mice with Duchenne muscular dystrophy.JCI insight · 2022Article
- Evaluation of the DBA/2J mouse as a potential background strain for genetic models of cardiomyopathy.Journal of molecular and cellular cardiology plus · 2022Article
- Shrinkage Properties and Their Relationship with Degradation of Proteins Linking the Endomysium and Myofibril in Lamb Meat Submitted to Heating or Air Drying.Foods (Basel, Switzerland) · 2022Article
- Drug development progress in duchenne muscular dystrophy.Frontiers in pharmacology · 2022Review
- Assessing the Use of the sGC Stimulator BAY-747, as a Potential Treatment for Duchenne Muscular Dystrophy.International journal of molecular sciences · 2021Article
- PDE10A Inhibition Reduces the Manifestation of Pathology in DMD Zebrafish and Represses the Genetic Modifier PITPNA.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Role of the Renin-Angiotensin-Aldosterone System in Dystrophin-Deficient Cardiomyopathy.International journal of molecular sciences · 2020Review
- Review
- Teaching an Old Molecule New Tricks: Drug Repositioning for Duchenne Muscular Dystrophy.International journal of molecular sciences · 2019Review
- Effects of PDE5 inhibition on dystrophic muscle following an acute bout of downhill running and endurance training.Journal of applied physiology (Bethesda, Md. : 1985) · 2019Article
- Discovery of Novel Therapeutics for Muscular Dystrophies using Zebrafish Phenotypic Screens.Journal of neuromuscular diseases · 2019Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundCardiomyopathy is a leading cause of mortality among Duchenne muscular dystrophy patients and lacks effective therapies. Phosphodiesterase type 5 is implicated in dystrophic pathology, and the phosphodiesterase type 5 inhibitor tadalafil has recently been studied in a clinical trial for Duchenne muscular dystrophy. METHODS AND
resultsTadalafil was evaluated for the prevention of cardiomyopathy in the mdx mouse and golden retriever muscular dystrophy dog models of Duchenne muscular dystrophy. Tadalafil blunted the adrenergic response in mdx hearts during a 30-minute dobutamine challenge, which coincided with cardioprotective signaling, reduced induction of μ-calpain levels, and decreased sarcomeric protein proteolysis. Dogs with golden retriever muscular dystrophy began daily tadalafil treatment prior to detectable cardiomyopathy and demonstrated preserved cardiac function, as assessed by echocardiography and magnetic resonance imaging at ages 18, 21, and 25 months. Tadalafil treatment improved golden retriever muscular dystrophy histopathological features, decreased levels of the cation channel TRPC6, increased total threonine phosphorylation status of TRPC6, decreased m-calpain levels and indicators of calpain target proteolysis, and elevated levels of utrophin. In addition, we showed that Duchenne muscular dystrophy patient myocardium exhibited increased TRPC6, m-calpain, and calpain cleavage products compared with control human myocardium.
conclusionsProphylactic use of tadalafil delays the onset of dystrophic cardiomyopathy, which is likely attributed to modulation of TRPC6 levels and permeability and inhibition of protease content and activity. Consequently, phosphodiesterase type 5 inhibition is a candidate therapy for slowing the development of cardiomyopathy in Duchenne muscular dystrophy patients.
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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.