ACE-031 (ACVR2B-Fc)

Myostatin Inhibitor | Experimental Muscle Growth

Half-life: 12-15 days

4 studies

2017 latest

Emerging

Dose 0.5-3 mg/kg IV every 2 weeks (clinical research doses only)

Frequency Every 2 weeks

Cycle Clinical trials used 4-12 week treatment periods

Storage 2-8°C; protect from light. Not commercially available.

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ACE-031 is a soluble form of the activin type IIB receptor (ActRIIB) fused to an IgG1 Fc domain. It functions as a decoy receptor, binding and neutralizing myostatin and other TGF-beta superfamily members that normally limit muscle growth. Originally developed by Acceleron Pharma for Duchenne muscular dystrophy (DMD), ACE-031 reached Phase 2 clinical trials before development was halted due to vascular side effects including nosebleeds and telangiectasia. In healthy volunteers, a single dose produced significant increases in lean mass and reductions in fat mass within 29 days.

Mechanism of Action

ACE-031 acts as a ligand trap for members of the TGF-beta superfamily. By mimicking the extracellular domain of the ActRIIB receptor, it intercepts myostatin (GDF-8), activin A, activin B, and GDF-11 before they can bind cell-surface receptors and activate Smad2/3 signaling. Blocking this pathway removes the natural brake on muscle protein synthesis and satellite cell proliferation, resulting in rapid skeletal muscle hypertrophy. The Fc fusion domain extends circulating half-life through FcRn-mediated recycling and provides bivalent ligand binding.

01 Significant lean mass increases (up to 1.7% in 29 days) observed in Phase 1 trials

02 Simultaneous reduction in fat mass alongside muscle gains

03 Long half-life (12-15 days) allows infrequent dosing

04 Broad TGF-beta ligand neutralization for robust anti-catabolic effects

05 Dose-dependent increases in thigh muscle volume confirmed by MRI

Molecular Data

Type

Soluble activin receptor type IIB-Fc fusion protein

Peak 0.0 mcg

Trough 0.0 mcg

SS Peak 0.0 mcg

SS Trough 0.0 mcg

Research Indications

Muscle Growth

Muscle Hypertrophy most effective

Phase 1 data showed statistically significant lean mass increases (average +1.7%) after a single IV dose in healthy postmenopausal women.

Muscular Dystrophy effective

Phase 2 trial in DMD patients showed improvements in lean body mass and bone mineral density, but trial was halted due to vascular adverse events.

Muscle Wasting / Cachexia effective

Preclinical models demonstrate robust prevention of muscle loss in disease states through myostatin pathway inhibition.

Body Composition

Fat Loss effective

Phase 1 trial subjects showed concurrent fat mass reductions alongside lean mass gains, suggesting favorable nutrient partitioning.

Bone Density moderate

DMD trial data showed increases in bone mineral density, consistent with known effects of ActRIIB pathway modulation on bone metabolism.

Dosing Protocols

Administered as an intravenous infusion in clinical trials. Research doses ranged from 0.1 to 3 mg/kg given every 2 weeks. This compound is not commercially available and has never been approved for any indication.

Goal	Dose	Frequency	Route
Phase 1 Research Protocol (Healthy Volunteers)	0.1-3 mg/kg	Single IV dose	IV infusion
Phase 2 Research Protocol (DMD)	0.5-2.5 mg/kg	Every 2 weeks	IV or SubQ

Interactions

Follistatin

Both inhibit myostatin through different mechanisms (ligand trapping vs. direct binding). Conceptually synergistic, but no clinical data on combination use.

synergistic

YK-11

Both target the myostatin pathway. YK-11 acts as a myostatin inhibitor through a different mechanism. Combined use could produce excessive pathway suppression with unpredictable effects.

monitor

What to Expect

Week 1-2

Initial ligand trapping begins; circulating myostatin levels decrease. No overt physical changes expected yet.

Week 2-4

Measurable lean mass increases detectable by DXA/MRI. Phase 1 data showed +1.7% lean mass by day 29. Possible onset of vascular side effects (nosebleeds).

Week 4-8

Continued muscle accretion with repeated dosing. Fat mass reduction becomes more apparent. Monitor closely for telangiectasia and bleeding events.

Post-treatment

Effects diminish over several weeks as drug clears. Muscle gains may partially persist with continued resistance training.

Side Effects & Safety

Common Side Effects

Nosebleeds (epistaxis) - most frequently reported adverse event
Gum bleeding
Telangiectasia (dilated small blood vessels visible on skin)
Skin erythema (redness)
Minor injection site reactions

Stop Signs - Discontinue if:

Recurrent or severe nosebleeds
Development of new or worsening telangiectasia
Unexplained bleeding from any site
Signs of hereditary hemorrhagic telangiectasia-like syndrome
Severe skin reactions or widespread erythema

Contraindications

NEVER approved for human use - clinical development discontinued
History of bleeding disorders or vascular malformations
Concurrent anticoagulant or antiplatelet therapy
Known hypersensitivity to Fc fusion proteins
Pregnancy or breastfeeding

Quality Checklist

Good Signs

Manufactured under GMP conditions for clinical trials
Characterized by SDS-PAGE and mass spectrometry
Endotoxin-tested and sterility-verified
Stored at 2-8°C with documented cold chain

Warning Signs

Clinical development halted - not commercially manufactured
No legitimate commercial source exists
Any product sold as ACE-031 is of unknown origin and quality
Fusion protein structure is sensitive to degradation

Bad Signs

Vascular side effects led to trial discontinuation - nosebleeds and telangiectasia were dose-limiting
Broad ligand trapping may cause unintended effects beyond myostatin inhibition
Long-term safety profile completely unknown

References

A soluble activin receptor type IIB (ACE-031) increases lean body mass and muscle strength in healthy postmenopausal women

Attie KM, Borgstein NG, Yang Y, Condon CH, Wilson DM, Pearsall AE, Kumar R, Willins DA, Seehra JS, Sherman ML

Journal of Clinical Endocrinology & Metabolism (2013)

Single ascending-dose Phase 1 trial in 48 postmenopausal women. ACE-031 produced statistically significant increases in total body lean mass (+1.7%) and thigh muscle volume (+5.1%) by day 29, with concurrent decreases in fat mass and leptin.
A phase 2 trial of ACE-031, a soluble activin receptor type IIB, in boys with Duchenne muscular dystrophy

Campbell C, McMillan HJ, Mah JK, Tarnopolsky M, Selby K, McClure T, Wilson DM, Sherman ML, Bhatt SA, Trachtenberg FL, Kunkel LM, Bhatt RS

Neuromuscular Disorders (2017)

Phase 2 study in 12 DMD boys showed increases in lean body mass and bone mineral density. Trial was halted due to safety concerns including epistaxis, telangiectasia, and erythema. Preliminary efficacy signals were observed but could not be fully evaluated.
Pharmacokinetic, pharmacodynamic, and safety results from a first-in-human study of ACE-031, a novel activin receptor type IIB/Fc fusion protein

Bhatt RS, Goss A, Wilson DM, Borgstein NG, Sherman ML

Journal of Clinical Pharmacology (2014)

ACE-031 demonstrated a half-life of approximately 12 days with dose-proportional pharmacokinetics. The compound suppressed circulating FSH levels, consistent with activin A neutralization, and showed a dose-dependent increase in lean mass biomarkers.
Myostatin inhibition in health and disease

Lee SJ

Annual Review of Cell and Developmental Biology (2004)

Comprehensive review establishing myostatin as a key negative regulator of skeletal muscle mass. Demonstrated that myostatin-null mice exhibit dramatic increases in muscle mass, providing the biological rationale for therapeutic myostatin inhibition strategies including soluble receptor approaches.

Disclaimer

This information is for educational and research purposes only. Consult a healthcare professional before use.