Key papers ✓ 4✗ 1~ 1

• ~ Mixed human RCTMuscle Nerve · 2017

  Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial.

  Humanssize not reportedRandomizedPlacebo-controlledDouble-blind

  Randomized, double-blind, placebo-controlled, ascending-dose trial; ACE-031 given subcutaneously every 2-4 weeks

  In a randomized, double-blind, placebo-controlled ascending-dose trial in ambulatory boys with Duchenne muscular dystrophy, ACE-031 showed non-significant trends toward preserved 6-minute walk distance, higher lean mass and bone density and lower fat mass, but the study was stopped after the second dosing regimen because of epistaxis and telangiectasias.

  Key resultNon-significant trend for maintained 6MWT distance in ACE-031 groups vs a decline with placebo; trends toward higher lean mass and BMD and lower fat mass

  Study details

  Studied

  Ambulatory boys with Duchenne muscular dystrophy

  Compared with

  Placebo

  Main outcome

  Safety (primary); pharmacokinetics, pharmacodynamics, 6-minute walk test, lean mass, fat mass, BMD (secondary)

  Sample

  Number of boys not stated in abstract

  Authors' conclusion

  ACE-031 showed pharmacodynamic trends; the study was stopped after the second dosing regimen because of epistaxis and telangiectasias. Myostatin inhibition is called a promising approach for DMD.

  Limitations

  Stopped early for safety concerns; efficacy trends not statistically significant.

  DOI 10.1002/mus.25268PubMed 27462804
• ✓ Positive human RCTMuscle Nerve · 2013

  A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers.

  Humans48 peopleRandomizedPlacebo-controlledDouble-blindLean mass and thigh volume assessed at day 29

  Double-blind, placebo-controlled single ascending-dose study (0.02-3 mg/kg s.c.)

  In 48 healthy postmenopausal women given a single dose of ACE-031 or placebo, the 3 mg/kg group gained 3.3% total body lean mass and 5.1% thigh muscle volume by day 29; the main adverse event was injection-site redness.

  Key resultAt 3 mg/kg, total body lean mass +3.3% (P = 0.03, DXA) and thigh muscle volume +5.1% (P = 0.03, MRI) at day 29

  Study details

  Studied

  Healthy postmenopausal women

  Compared with

  Placebo

  Main outcome

  Safety, pharmacokinetics, pharmacodynamics (lean mass by DXA, thigh muscle volume by MRI)

  Sample

  48 healthy postmenopausal women, randomized 3:1 to ACE-031 or placebo

  Authors' conclusion

  Single-dose ACE-031 was generally well tolerated and increased muscle mass in healthy postmenopausal women.

  Limitations

  Single dose, healthy volunteers.

  DOI 10.1002/mus.23539PubMed 23169607
• ✓ Positive animalPLoS One · 2026

  ACE-031, a soluble activin type IIB receptor, increases muscle mass and strength in the common marmoset (Callithrix jacchus).

  Animalssize not reportedRandomizedSham/vehicle control14 weeks

  Randomized ACE-031 vs vehicle

  In common marmosets randomized to 14 weeks of ACE-031 or vehicle, treated animals gained lean body mass and showed larger type I and type II fibres and greater absolute and specific muscle force.

  Key resultSignificant time x treatment interaction for lean body mass (ACE-031 greater at euthanasia than baseline; not seen in vehicle controls); increased type I and II fiber cross-sectional area in biceps brachii and increased absolute and specific EDL force

  Study details

  Studied

  Common marmosets (Callithrix jacchus)

  Compared with

  Vehicle (10 mM Tris buffered saline)

  Main outcome

  Lean body mass, fiber cross-sectional area, ex vivo muscle force

  Sample

  Number of marmosets not stated in abstract

  Authors' conclusion

  Efficacy in non-human primates provides optimism that targeting multiple negative regulators of skeletal muscle may help treat human myopathies.

  Limitations

  Animal study; sample size not stated in abstract.

  DOI 10.1371/journal.pone.0342666PubMed 41686840Free full text
  Fig 1 Fig 3
• ✓ Positive animalbioRxiv · 2025

  ACE-031, a Soluble Activin Type IIB Receptor, Increases Muscle Mass and Strength in the Common Marmoset (Callithrix jacchus).

  Animalssize not reportedRandomizedSham/vehicle control14 weeks

  Randomized ACE-031 vs vehicle (preprint)

  Preprint of the same marmoset experiment, reporting increased body weight, lean mass, fibre cross-sectional area and ex vivo force with ACE-031.

  Key resultSignificant increase in body weight and lean body mass from baseline with ACE-031, none in vehicle controls; increased type I and II fiber CSA and EDL absolute and specific force

  Study details

  Studied

  Common marmosets (Callithrix jacchus)

  Compared with

  Vehicle (10 mM Tris buffered saline)

  Main outcome

  Body weight, lean body mass, fiber cross-sectional area, ex vivo muscle force

  Sample

  Number of marmosets not stated in abstract

  Authors' conclusion

  Efficacy in non-human primates provides optimism that targeting multiple negative regulators of skeletal muscle may help treat human myopathies.

  Limitations

  Animal study; preprint; sample size not stated in abstract.

  DOI 10.1101/2025.10.01.679778PubMed 41256654Free full text
• ✗ Negative animalMol Ther · 2014

  Blockade of ActRIIB signaling triggers muscle fatigability and metabolic myopathy.

  Animalssize not reported4 months

  4-month pharmacological blockade of ActRIIB signaling with soluble ActRIIB-Fc

  Four months of soluble ActRIIB-Fc in mice caused extreme muscle fatigability, raised serum lactate, reduced muscle capillarization and a severe metabolic myopathy in the mdx model; the authors caution against this strategy as a sole treatment.

  Study details

  Studied

  Mice including the mdx model of Duchenne muscular dystrophy

  Main outcome

  Muscle fatigability, serum lactate, muscle energy metabolism

  Authors' conclusion

  ActRIIB blockade triggered extreme muscle fatigability and a severe metabolic myopathy in mdx mice; the authors caution against deploying this strategy, at least in isolation, for neuromuscular disorders.

  Limitations

  Mouse study; uses soluble ActRIIB-Fc rather than ACE-031 itself.

  DOI 10.1038/mt.2014.90PubMed 24861054Free full text
• ✓ Positive animalJ Appl Physiol (1985) · 2010

  Administration of a soluble activin type IIB receptor promotes skeletal muscle growth independent of fiber type.

  Animalssize not reportedSham/vehicle control28 days

  ACE-031 vs vehicle control

  In mice, 28 days of ACE-031 increased body weight 16% and individual muscle weights 26-46% and enlarged both type I and type II fibres.

  Key resultBody weight 16% greater than control; soleus, plantaris, gastrocnemius and EDL weights up 33, 44, 46 and 26% (P<0.05); fiber CSA up 22% (type I) and 28% (type II) in soleus

  Study details

  Studied

  8-week-old C57BL/6 mice

  Compared with

  Vehicle

  Main outcome

  Body weight, muscle wet weight, fiber cross-sectional area and fiber type

  Authors' conclusion

  ACE-031 increased muscle mass independent of fiber type, providing optimism it may be a viable therapeutic for musculoskeletal diseases.

  Limitations

  Short duration; effects may be age dependent (authors call for confirmation).

  DOI 10.1152/japplphysiol.00866.2009PubMed 20466801Free full text

Reported side effects

• reportedNosebleeds (epistaxis) [ref]
• reportedTelangiectasias (dilated small blood vessels) [ref]
• reportedInjection-site redness [ref]

The Duchenne trial was halted early over bleeding and vascular side effects and clinical development was discontinued.

4 registered human trials (0 active)

✓ positive · ✗ negative · ~ mixed · ? inconclusive, judged on each paper's own main outcome. Grades: A strong human evidence → D little or none. Papers and verdicts are drawn from PubMed, Europe PMC and Russian journals (CyberLeninka); not medical advice.