ArticleProceedings of the National Academy of Sciences of the United States of America2017
Blockade of activin type II receptors with a dual anti-ActRIIA/IIB antibody is critical to promote maximal skeletal muscle hypertrophy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 133 citations in OpenAlex.
- GDF8 and activin A are the key negative regulators of muscle mass in postmenopausal females: a randomized phase I trial.Nature communications · 2025Trial
- Safety and pharmacokinetics of bimagrumab in healthy older and obese adults with body composition changes in the older cohort.Journal of cachexia, sarcopenia and muscle · 2020Trial
- Bimagrumab vs Optimized Standard of Care for Treatment of Sarcopenia in Community-Dwelling Older Adults: A Randomized Clinical Trial.JAMA network open · 2020Trial
- Exerkines in precision management of metabolic diseases.Chinese medical journal · 2026Review
- Targeting the activin/myostatin - actrii pathway to preserve skeletal muscle mass in obesity: mechanistic insights and therapeutic perspectives.Reviews in endocrine & metabolic disorders · 2026Review
- Putting the brakes on muscle growth: Myostatin as regulator of disuse atrophy.Experimental physiology · 2026Review
- A Lineup for Next Anti-Obesity Medicines: Beyond Incretin-Based Pharmacotherapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Exercise-induced myokines in metabolic regulation: mechanisms, mimetics, and translational potential.Archives of pharmacal research · 2026Review
- A skeletal muscle atlas shows neuromuscular junction adaptations to growth and atrophy.Developmental cell · 2026Article
- Management of Obese Patients with Cardiovascular Disease with Emerging Weight-Lowering Drugs: A Narrative Review.Biomedicines · 2026Review
- ActIIR inhibition improves motor outcome and preserves muscle fibers after experimental autoimmune neuritis.Acta neuropathologica communications · 2026Article
- Article
- ACE-031, a soluble activin type IIB receptor, increases muscle mass and strength in the common marmoset (Callithrix jacchus).PloS one · 2026Article
- High-fat diet induced obesity and anti-activin receptor antibody: Effects on bone properties in mice.Bone reports · 2025Article
- Are we giving too much weight to lean mass loss?Molecular metabolism · 2025Review
- Signaling networks governing skeletal muscle growth, atrophy, and cachexiaSkeletal muscle · 2025Review
- Current Perspectives on GLP-1 Agonists in Contemporary Clinical Practice from Science and Mechanistic Foundations To Optimal Translation.Current atherosclerosis reports · 2025Review
- ACE-031, a Soluble Activin Type IIB Receptor, Increases Muscle Mass and Strength in the Common Marmoset (Callithrix jacchus).bioRxiv : the preprint server for biology · 2025Article
- Impact of myokines on chronic liver diseases: exploring the effects of metabolic dysfunction-associated steatotic liver disease (MASLD) on skeletal muscle. A narrative review.European journal of translational myology · 2025Article
- Cancer therapy and cachexia.The Journal of clinical investigation · 2025Review
28 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The TGF-β family ligands myostatin, GDF11, and activins are negative regulators of skeletal muscle mass, which have been reported to primarily signal via the ActRIIB receptor on skeletal muscle and thereby induce muscle wasting described as cachexia. Use of a soluble ActRIIB-Fc "trap," to block myostatin pathway signaling in normal or cachectic mice leads to hypertrophy or prevention of muscle loss, perhaps suggesting that the ActRIIB receptor is primarily responsible for muscle growth regulation. Genetic evidence demonstrates however that both ActRIIB- and ActRIIA-deficient mice display a hypertrophic phenotype. Here, we describe the mode of action of bimagrumab (BYM338), as a human dual-specific anti-ActRIIA/ActRIIB antibody, at the molecular and cellular levels. As shown by X-ray analysis, bimagrumab binds to both ActRIIA and ActRIIB ligand binding domains in a competitive manner at the critical myostatin/activin binding site, hence preventing signal transduction through either ActRII. Myostatin and the activins are capable of binding to both ActRIIA and ActRIIB, with different affinities. However, blockade of either single receptor through the use of specific anti-ActRIIA or anti-ActRIIB antibodies achieves only a partial signaling blockade upon myostatin or activin A stimulation, and this leads to only a small increase in muscle mass. Complete neutralization and maximal anabolic response are achieved only by simultaneous blockade of both receptors. These findings demonstrate the importance of ActRIIA in addition to ActRIIB in mediating myostatin and activin signaling and highlight the need for blocking both receptors to achieve a strong functional benefit.
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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.