reviewed april 2026|next review october 2026|88 physicians psi has verified|543 published studies
ACE-031
ACE-031 is a soluble activin receptor type IIB (ActRIIB-Fc) fusion protein that traps myostatin and related ligands, with Phase I data showing lean mass gains but a Duchenne muscular dystrophy trial halted due to vascular safety signals.
Evidence landscape: 543 published studies
543 published items. 18 human studies and 166 animal studies.
- 18 Human
- 166 Animal
- 16 Reviews
- 343 Other research
Not FDA-approved. Clinical development was paused after vascular safety signals (epistaxis, gum bleeding, telangiectasias) in a Duchenne muscular dystrophy trial. Developed by Acceleron Pharma.
Not available through any commercial or specialty pharmacy channel. Clinical development is paused. A successor molecule (ACE-2494) has been in development.
ACE-031 is a soluble ActRIIB-Fc fusion protein that traps myostatin, activin A, GDF-11, and other TGF-beta superfamily ligands. The broad ligand trapping caused off-target vascular effects. The related compound luspatercept (ActRIIA-Fc) achieved FDA approval for anemia, validating the receptor-trap platform.
PSI Assessment
ACE-031 validated the central hypothesis of the myostatin inhibition field: blocking the ActRIIB receptor produces rapid, measurable muscle growth in humans. It also demonstrated why broad receptor blockade is dangerous. Phase I data in healthy postmenopausal women showed dose-dependent lean mass increases. A subsequent Duchenne muscular dystrophy (DMD) trial was halted after vascular safety signals including epistaxis (nosebleeds), gum bleeding, and skin telangiectasias. The muscle-building effect was real. The safety profile was unacceptable. The distinction between ACE-031's scientific validation and clinical failure is critical for understanding the entire myostatin inhibitor field.
Phase I lean mass increase in healthy women. DMD trial halted for vascular safety. Broad ligand trapping produces off-target effects beyond muscle.
The mechanism is a soluble ActRIIB-Fc fusion protein that acts as a decoy receptor, sequestering myostatin, activin A, GDF-11, and other TGF-beta superfamily ligands in the circulation. By preventing these ligands from binding to cell surface ActRIIB receptors, it removes the braking mechanism on muscle growth. The problem was specificity: ActRIIB binds many ligands beyond myostatin, and blocking all of them produced vascular side effects. The related compound luspatercept (ActRIIA-Fc, targeting the closely related ActRIIA receptor) succeeded for a different indication entirely (anemia), achieving FDA approval under the brand name Reblozyl. This demonstrated that the receptor-trap platform works pharmacologically but that the therapeutic window depends critically on which receptor is targeted and which ligands are trapped.
What the evidence supports
Phase I trial demonstrated measurable lean muscle mass increases in healthy postmenopausal women. The soluble ActRIIB-Fc mechanism traps myostatin and related TGF-beta superfamily ligands. The related compound luspatercept (ActRIIA-Fc) achieved FDA approval for anemia, validating the receptor-trap platform.
What is not yet established
Whether ACE-031 can be safely used for muscle-building given the vascular safety signals that halted the DMD trial. Whether more selective myostatin targeting avoids the off-target effects of broad ActRIIB ligand trapping. Whether the muscle gains observed in Phase I translate to functional outcomes.
Research Evidence
The findings below cover the clinical evidence that both validated myostatin inhibition and demonstrated why ACE-031 specifically was not viable.
Evidence by condition
Evidence dimensions available for each condition ACE-031 has been studied for.
| Condition | Mechanism | Animal evidence | Human evidence | Replication |
|---|---|---|---|---|
| Muscle Wasting | ||||
| Duchenne Muscular Dystrophy | ||||
| Neuromuscular Disease |
Phase I trial in healthy postmenopausal women demonstrated dose-dependent lean muscle mass increases with ACE-031. The muscle-building effect confirmed that ActRIIB ligand trapping produces rapid anabolic effects in humans.
This was the first clinical demonstration that blocking myostatin pathway signaling increases muscle mass in humans. The finding validated the entire field. The safety profile became the limiting factor.
18 Human|166 Animal|16 Reviews
View all 543 indexed studiesHow ACE-031 Works
ACE-031 is a recombinant fusion protein consisting of the extracellular domain of activin receptor type IIB (ActRIIB) fused to the Fc domain of human IgG1. It acts as a soluble decoy receptor, sequestering myostatin, activin A, GDF-11, and other TGF-beta family ligands.
Soaks up myostatin like a sponge before it reaches muscles. Without myostatin signaling, the muscle growth brake is released. The problem was that it soaked up too many other signaling molecules too, causing vascular side effects.
For a more detailed view of the biology, here is what researchers have observed at the molecular level.
Recombinant ActRIIB-Fc fusion protein. Binds myostatin, activin A, GDF-11, and other TGF-beta superfamily ligands. Broad ligand binding caused off-target vascular effects including epistaxis and telangiectasias.
What is ACE-031 being studied for?
Researchers are studying ACE-031 across several health conditions. Each condition below is labeled with the strength of evidence that exists for that specific use, not for ACE-031 overall. This means a compound can have human studies for one condition but only animal data for another.
Muscle Wasting
·Human TrialsPhase I trial demonstrated dose-dependent lean mass increases in healthy postmenopausal women. The anabolic effect was rapid and measurable. This was the first human proof of concept for ActRIIB-mediated muscle growth.
Limitations: Development paused due to vascular safety signals. Whether the muscle gains translate to functional outcomes was not assessed.
Duchenne Muscular Dystrophy
·Animal StudiesA clinical trial in DMD patients was initiated based on the Phase I muscle mass data. The trial was halted after vascular safety signals including epistaxis, gum bleeding, and telangiectasias.
Limitations: Trial halted for safety. The vascular effects likely reflect broad ActRIIB ligand trapping beyond myostatin (activin A and GDF-11 play roles in vascular biology).
Neuromuscular Disease
·Animal StudiesThe ActRIIB ligand-trapping mechanism has animal study support for multiple neuromuscular conditions. Clinical translation was blocked by the safety profile.
Limitations: No completed efficacy trials. The safety signals from the DMD trial apply to any ACE-031 indication.
Safety and Regulatory Status
FDA Status: Not FDA-approved. Clinical development paused after vascular safety signals in DMD trial. Epistaxis (nosebleeds), gum bleeding, and skin telangiectasias were reported.
Availability: Not available through any channel. Clinical development is paused. Not available through pharmacies or research suppliers.
Class context: The vascular safety signals likely reflect on-target effects of broad ActRIIB ligand trapping. Activin A and GDF-11 play roles in vascular biology. The related compound luspatercept (targeting ActRIIA) achieved FDA approval for anemia, suggesting receptor selectivity determines the safety window.
ACE-031 failed on safety, not efficacy. The vascular side effects (epistaxis, gum bleeding, telangiectasias) are likely inherent to broad ActRIIB ligand trapping rather than an off-target effect. This is why the field has moved toward more selective approaches (bimagrumab targets ActRII with different selectivity, myostatin-specific antibodies target a single ligand).
Peptide Structure
Technical molecular data for researchers and clinicians.
Questions and Comparisons
Questions the evidence raises for a ACE-031 discussion.
Comparison and Related Research
ACE-031 sits within the myostatin pathway inhibitor field. Understanding alternative approaches clarifies why ACE-031 was abandoned and what replaced it.
Related compounds
Frequently Asked Questions
References
Each citation links to the original study on PubMed, the U.S. National Library of Medicine database.
- 1.Phase I dose-escalation study in healthy postmenopausal women evaluating the safety and biological effects of ACE-031, a soluble form of the activin receptor type IIB. A single dose produced measurable increases in lean body mass and decreases in fat mass, along with increases in bone formation markers.Attie KM et al., 2013 in Muscle Nerve. View on PubMed
- 2.Randomized, placebo-controlled trial testing ACE-031 in boys with Duchenne muscular dystrophy. Although the compound showed biological activity including increased lean mass, the trial was halted due to safety concerns including nosebleeds and telangiectasias (small dilated blood vessels), which were attributed to the broad ligand-trapping activity of the molecule.Campbell C et al., 2017 in Muscle Nerve. View on PubMed
- 3.Biochemical study characterizing how the extracellular domain of the activin type IIB receptor (the basis for ACE-031) binds to multiple TGF-beta superfamily ligands including myostatin, activin A, and GDF-11. This work helped explain both the muscle-building effects and the broad biological activity that led to off-target effects in clinical trials.Sako D et al., 2010 in J Biol Chem. View on PubMed
- 4.Identified multiple ligands that bind soluble ActRIIB using proteomic approaches, and validated their roles in muscle mass regulation. The study established the mechanistic foundation for how ActRIIB-based inhibitors like ACE-031 promote muscle growth by blocking multiple negative regulators simultaneously.Souza TA et al., 2008 in Mol Endocrinol. View on PubMed
Medical Disclaimer
This content is for educational and informational purposes only and does not constitute medical advice. The information presented reflects published research as indexed by PSI and should not be used to make treatment decisions. Always consult a qualified healthcare provider before starting, stopping, or modifying any treatment.