ACE-031
Also known as: ACE031, Ramatercept, ActRIIB-Fc
3 notable studies · 4 references
TLDR
ACE-031 is an experimental soluble ActRIIB-Fc ligand trap that increased muscle mass in controlled human studies by blocking myostatin and related activin-family signals, but its Duchenne muscular dystrophy program was halted after vascular adverse effects including telangiectasias and nosebleeds emerged, leaving its clinical risk-benefit profile unresolved.
Research Supports
- Studied for effects on skeletal muscle mass and lean body mass
- Investigated as a potential treatment for Duchenne muscular dystrophy
- Examined for effects on muscle strength and force production
- Studied for effects on bone metabolism
- Investigated for vascular safety signals
Observations Reported in Research
- Increased total-body lean mass 3.3% and thigh-muscle volume 5.1% by day 29 in healthy postmenopausal women (Attie et al., 2013)
- Showed trends toward increased lean mass and bone mineral density in boys with DMD, without a statistically significant change in six-minute walk distance (Campbell et al., 2017)
- DMD trial was stopped after safety concerns involving telangiectasias and nosebleeds
- Increased lean mass, muscle-fiber size, and ex-vivo muscle force in common marmosets (Cadena et al., 2026)
These are brief summaries of what the referenced research examined or reported — not conclusions about safety or effectiveness, and not medical advice. See Notable Studies and Sources & References below for the full context and citations.
At a Glance
Classification: Recombinant soluble activin receptor type IIB fusion protein; ligand trap; myostatin/activin-pathway inhibitor
ACE-031 is not a peptide in the conventional sense. It is an engineered fusion protein composed of: extracellular portion of human activin receptor type IIB (ActRIIB) • human IgG1 Fc domain. It essentially acts as a circulating decoy receptor. Instead of myostatin and related ligands binding cellular ActRIIB receptors, ACE-031 captures them in circulation. The result: less negative regulation of skeletal muscle. Unlike many research-market compounds, ACE-031 actually reached randomized human trials. A single dose increased lean mass and thigh-muscle volume in healthy postmenopausal women. It was subsequently studied in boys with Duchenne muscular dystrophy. But development hit an important problem: The DMD trial was stopped because of safety concerns involving nosebleeds and telangiectasias. That makes ACE-031 an excellent example of why: more muscle ≠ successful medicine.
What Is ACE-031?
ACE-031 is a recombinant ActRIIB-Fc fusion protein. Think of the normal pathway as: Myostatin / Activin ↓ cell-surface ActRIIB ↓ SMAD signaling ↓ restrained skeletal-muscle growth. ACE-031 places a soluble version of the receptor into circulation: Myostatin / Activin ↓ captured by ACE-031 ↓ less ligand reaches cellular ActRIIB ↓ less growth-inhibitory signaling ↓ increased muscle-growth potential. The Fc component extends the molecule's circulating lifetime. In the human Phase 1 study, the mean half-life was approximately 10–15 days.
What Are Researchers Studying?
Skeletal muscle mass
This is ACE-031's central biological effect. In a randomized single-dose trial involving 48 healthy postmenopausal women, the highest tested dose produced: +3.3% total-body lean mass and +5.1% thigh-muscle volume by day 29. That's direct controlled human evidence that broad ActRIIB ligand trapping can increase measurable muscle mass. But: muscle volume ≠ strength ≠ athletic performance ≠ improved clinical function.
Duchenne muscular dystrophy
ACE-031 was developed as a possible treatment for muscle-wasting diseases including DMD. A randomized placebo-controlled study evaluated repeated administration in ambulatory boys with DMD. Researchers observed trends toward: • Increased lean mass • Increased bone mineral density • Reduced fat mass • Preservation of six-minute walk distance. However, the functional difference did not reach statistical significance, and development was interrupted by safety findings.
Myostatin inhibition
ACE-031 is commonly called a myostatin inhibitor. Again, that's incomplete. ACE-031 traps multiple ActRIIB ligands, including myostatin and activins. That broad activity probably helps explain why its muscle effect can be substantial. It may also explain why unexpected effects appeared in other tissues.
Muscle strength
One critical question is whether ActRIIB blockade produces functional muscle rather than simply larger muscle. A newly published 2026 common-marmoset study adds useful evidence here. ACE-031 increased lean body mass and muscle-fiber size, and treated animals showed increases in ex-vivo muscle force production. This is notable new evidence, but it remains nonhuman-primate research.
Bone metabolism
ActRIIB-family signaling also affects bone. The healthy-volunteer trial observed changes in biomarkers consistent with effects on bone metabolism, while the DMD study reported trends toward increased bone mineral density. This reinforces a recurring theme: ACE-031 doesn't manipulate a muscle-only pathway.
Vascular biology
This became the major clinical warning signal. In the DMD trial, researchers observed: • Telangiectasias • Epistaxis / nosebleeds particularly with the higher repeated-dose regimen. These effects were reversible, but they suggested that trapping ActRIIB-family ligands was influencing vascular biology. The study was stopped after the second dosing regimen because of these potential safety concerns.
How Does It Work?
ACE-031 is essentially a ligand trap: ACE-031 ↓ binds circulating myostatin + activin-family ligands ↓ prevents efficient binding to cell-surface ActRIIB ↓ reduces downstream SMAD2/3 signaling ↓ removes part of the negative-growth signal ↓ increased skeletal-muscle growth. This is broader than blocking myostatin alone. That distinction is crucial.
What Does the Research Show?
Human research
ACE-031 has real randomized human research. Healthy adults 48 healthy postmenopausal women participated in a double-blind placebo-controlled single-dose study. At the highest dose, lean mass increased 3.3% and thigh-muscle volume increased 5.1% by day 29. Duchenne muscular dystrophy ACE-031 was then tested in ambulatory boys with DMD. The trial showed biological effects on body composition but was stopped because of vascular safety concerns. Functional outcomes were suggestive rather than conclusively positive. So the correct Aminodex conclusion is: ACE-031 clearly demonstrated biological activity in humans, but its original clinical-development program did not establish an acceptable successful therapy.
Animal research
Extensive animal research preceded human development. And interestingly, the translational story received a new addition in 2026. In common marmosets, ACE-031 increased: • Body weight • Lean mass • Muscle-fiber cross-sectional area • Absolute and specific muscle-force production. This provides strong confirmation that broad ActRIIB ligand trapping can generate functional muscle effects in a primate model. It doesn't erase the human safety findings.
In-vitro research
The molecular mechanism is well characterized: ACE-031 binds ligands that normally activate ActRIIB. Those include: • Myostatin / GDF-8 • Activins • Other related TGF-β-family ligands. This broad ligand profile distinguishes ACE-031 from more selective myostatin-blocking strategies.
Notable Studies
A Single Ascending-Dose Study of Muscle Regulator ACE-031 in Healthy Volunteers
humanForty-eight healthy postmenopausal women received one subcutaneous dose of ACE-031 or placebo. At 3 mg/kg, total-body lean mass increased approximately 3.3% and thigh-muscle volume approximately 5.1% by day 29. ACE-031 had a mean half-life of approximately 10–15 days.
Limitations: Single-dose, short-duration study in healthy postmenopausal women. Increased muscle mass does not establish long-term functional benefit or safety.
View publication →Myostatin Inhibitor ACE-031 Treatment of Ambulatory Boys With Duchenne Muscular Dystrophy: Results of a Randomized, Placebo-Controlled Clinical Trial
humanAmbulatory boys with DMD received repeated ACE-031 or placebo. Body-composition findings suggested increased lean mass and bone mineral density with reduced fat mass. Six-minute walking showed a favorable numerical trend but not a statistically significant treatment effect.
Limitations: The study was terminated after the second dosing regimen because of safety concerns involving epistaxis and telangiectasias, preventing a complete assessment of longer-term efficacy.
View publication →ACE-031, a Soluble Activin Type IIB Receptor, Increases Muscle Mass and Strength in the Common Marmoset
animalCommon marmosets received ACE-031 or vehicle for 14 weeks. ACE-031 increased lean body mass and skeletal-muscle fiber size and improved ex-vivo measures of muscle-force production.
Limitations: Nonhuman-primate research cannot resolve the safety and efficacy questions raised by previous human ACE-031 development.
View publication →What We Still Don't Know
• Whether a safe therapeutic window exists for chronic ACE-031 • Long-term vascular effects • Long-term cardiovascular safety • Long-term reproductive effects • Consequences of broad activin inhibition • Whether larger muscles consistently become stronger muscles in humans • Whether meaningful functional benefit can be achieved in muscle disease • Long-term bone effects • Whether alternative dosing could avoid telangiectasia and epistaxis • Cancer-related implications of prolonged pathway manipulation • Whether modern research-market ACE-031 actually corresponds to authentic pharmaceutical-development material. That last issue has direct evidence too. A 2025 analytical study examined 14 black-market ACE-031 products and found that only 12 contained an ACVR2B-immunoreactive protein. Even that does not establish correct structure, purity, biological activity or equivalence to clinical-trial ACE-031.
Related Compounds
Recent publications
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Sources & References
- Attie KM, et al. A Single Ascending-Dose Study of Muscle Regulator ACE-031 in Healthy Volunteers. Muscle & Nerve. 2013.
- Campbell C, et al. Myostatin Inhibitor ACE-031 Treatment of Ambulatory Boys With Duchenne Muscular Dystrophy. Muscle & Nerve. 2017.
- Cadena SM, et al. ACE-031, a Soluble Activin Type IIB Receptor, Increases Muscle Mass and Strength in the Common Marmoset. PLOS One. 2026.
- Gel Electrophoretic Detection of Black Market ACE-031.
Supplier Listings
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