One was tested, worked, and was stopped. The other has no human protein-injection trial.
ACE-031 increased lean mass in humans and its trial was terminated anyway, over nosebleeds and dilated skin vessels traced to a second protein it blocked by accident. Follistatin's human evidence comes from small gene therapy studies, and that is a different intervention from injecting the protein. Neither is approved. The lesson from ACE-031's failure produced a myostatin drug that works, and it is neither of these.
| Attribute | Follistatin | ACE-031 |
|---|---|---|
| What it is | A naturally occurring glycoprotein | An engineered receptor decoy, not a peptide [1] |
| How it blocks myostatin | Grabs the hormone itself | Blocks the receptor the hormone uses [1] |
| Human evidence | Small gene therapy studies [6] | |
| Injected protein tested in humans | No [6] | Yes [2] |
| Did it build muscle | Unknown in humans | Yes [2] |
| Status | Not approved, never submitted | Development discontinued 2013 [4] |
ACE-031 was stopped despite working. A narrower molecule succeeded later.
Follistatin is a natural glycoprotein that binds myostatin directly. ACE-031 is an engineered decoy receptor that catches anything headed for the ActRIIB receptor. Both aim to remove the brake on muscle growth, one level apart.
A glycoprotein your body makes that binds myostatin and holds it out of action. Myostatin is the brake on muscle growth, so removing it should let muscle grow. In plain terms: a natural molecule that grabs the brake and holds it.
A laboratory-built fusion of part of a receptor stuck to an antibody fragment. It floats in the blood and soaks up anything that would have docked at that receptor. In plain terms: a decoy that catches myostatin before it reaches the muscle, and catches other things too.
One catches the hormone itself, and the other blocks the door it arrives through, which other hormones also use.
ACE-031 blocks the ActRIIB receptor, and BMP9 and BMP10 use that same receptor to keep blood vessels stable. Trial participants developed nosebleeds, bleeding gums and dilated skin vessels, and the trials were halted in 2011.
Muscle growth is held back by a hormone called myostatin. Remove it and muscle grows, as cattle, dogs, mice and a small number of people with natural myostatin mutations all demonstrate. Every compound in this category is trying to remove it.
There are two ways to do that, and they are not equivalent.
Follistatin works on the hormone. It binds myostatin directly and holds it inactive. Whatever else uses the same receptor is untouched, because follistatin never goes near it. It also binds activins, a related family, so it is not perfectly selective either.
ACE-031 works one level down, on the receptor. It is a soluble copy of the ActRIIB receptor fused to an antibody fragment, floating in the bloodstream and catching anything headed for that receptor. [1]
The problem is what else uses that door. ActRIIB is not myostatin's private entrance. BMP9 and BMP10 use it too, and those proteins keep blood vessels stable. Block the receptor and you block them alongside myostatin. [1][5]
That is what happened in the trials. Participants developed nosebleeds, bleeding gums, and small dilated blood vessels visible in the skin. [3][4]
The pattern was also recognisable. Those symptoms match hereditary haemorrhagic telangiectasia, a genetic bleeding disorder. Loss-of-function mutations in BMP9 were subsequently confirmed as a cause of that disorder in humans. [5]
So the side effect was not bad luck. The drug reproduced a known genetic disease by blocking the same signalling the disease disrupts.
It also binds activins. A narrower mechanism is not proof of safety.
Three signals caught before reaching the cell: the off-target problem.
| Attribute | Follistatin | ACE-031 |
|---|---|---|
| Also called | FS-344, follistatin-344 | Ramatercept, ActRIIB-Fc |
| Molecular type | Glycoprotein | Fusion protein, receptor extracellular domain plus IgG1 Fc |
| Made how | Recombinant, or delivered by gene therapy | Recombinant, in mammalian cell culture |
| Mechanism | Binds myostatin and activins | Decoy for the ActRIIB receptor |
| Off-target reach | Activins | |
| Half-life | Not established for the injected protein [6] | About 10 to 14 days [2] |
| Human trials | Gene therapy studies, including six-patient cohorts [6] | |
| Muscle effect in humans | Modest functional signal, open label [6] | Lean mass up a measurable lean-mass increase [2] |
| Why development stopped | Never started as an injectable drug | |
| Approved | No | No, discontinued 2013 [4] |
| What vendors sell | Recombinant protein or peptide fragments | Identity varies: tested black-market products were not the trial molecule [7] |
ACE-031's Phase 1 produced a measurable lean-mass increase in 48 women. Its Phase 2 in boys with Duchenne was terminated in 2011 and the programme abandoned in 2013. The 2015 Becker study delivered the gene by viral vector to six patients.
Myostatin is identified as the brake on muscle growth. Cattle and dogs with natural mutations in the gene are visibly more muscular, and the same has been documented in a small number of people. The category begins here.
Acceleron Pharma develops ACE-031, a soluble ActRIIB receptor fused to an antibody fragment, designed to trap myostatin before it reaches muscle. Shire partners on development. [4]
Phase 1 in 48 healthy postmenopausal women. Dose-dependent increases in lean body mass, up to a measurable lean-mass increase at the highest dose, with fat mass falling in the top dose group and bone formation markers rising. [2]
That result is the reason everything after it happened, because it showed the mechanism working in people.
Phase 2 in ambulatory boys with Duchenne muscular dystrophy, with an open-label extension. [3]
Both trials are stopped. Participants develop nosebleeds, bleeding gums and telangiectasias, small dilated blood vessels visible at the skin. The independent data monitoring committee cannot rule out worsening with continued exposure. The extension study is recorded on ClinicalTrials.gov as terminated based on preliminary safety data. [3]
The events resolved when dosing stopped. [4]
Loss-of-function mutations in BMP9 are confirmed as a cause of a human vascular anomaly and bleeding syndrome. [5] ACE-031 blocks BMP9 through the shared receptor, which explains the bleeding pattern directly.
Acceleron and Shire announce they have concluded their collaboration and will not restart the programme. Additional non-clinical and toxicology work had been done in the interim, and the companies stated the findings did not support further development. [4]
Mendell and colleagues publish a human follistatin gene-therapy study. Six patients with Becker muscular dystrophy, treated by AAV gene therapy, delivering the follistatin gene instead of injecting the protein. Open label, with a modest functional signal. [6]
Acceleron's successor molecule, engineered to avoid the off-target binding that stopped ACE-031, is approved as sotatercept, marketed as Winrevair, for pulmonary arterial hypertension. [8]
The lesson from the failure produced an approved drug. It was not the muscle indication.
Apitegromab, approved in September 2026 for spinal muscular atrophy, is an antibody that binds the inactive precursor of myostatin rather than the receptor or the active hormone, meets its primary endpoint in a Phase 3 trial in spinal muscular atrophy. 188 patients, with a 1.8 point difference on the motor function scale against placebo at 52 weeks. The vascular effects that stopped ACE-031 were not reported. [10]
By targeting the precursor, it leaves activin A, BMP9, BMP10 and TGF-beta alone. That is the specific engineering answer to the specific problem. [10]
ACE-031 is discontinued and sold online as a research chemical. Follistatin protein has no human injection trial located and is sold the same way.
Phase 1 showed a 3.3% lean-mass increase at the highest dose, with fat falling and bone markers rising. [2] By the standards of this category that is a real result in humans, and almost nothing else on this site can match it.
Then boys in the Phase 2 started getting nosebleeds. Not a vague safety signal: nosebleeds, bleeding gums, and spider veins in the skin, in a pattern that matched a known genetic bleeding disorder. [3][4] Two years of extra toxicology followed, and the sponsors concluded the findings did not support going on. [4]
All of which the mechanism accounts for. ACE-031 blocks a receptor, and myostatin is not the only thing that uses it. BMP9 and BMP10 come through the same door, and they keep blood vessels stable. [1][5]
The sequel is the part nobody tells. Acceleron went back and built a more selective molecule that avoided the off-target binding, and it is approved as Winrevair for a lung condition. [8]
Somebody else solved it for muscle. Apitegromab binds the inactive precursor of myostatin, sparing BMP9, BMP10 and activin A entirely. It met its Phase 3 endpoint in spinal muscular atrophy with no vascular effects of the sort that stopped ACE-031 reported. [10]
So the honest reading of ACE-031 is not that myostatin inhibition failed. Blocking a shared receptor was the wrong way in, and the field found a better one.
Follistatin binds myostatin itself, leaving the receptor free. ACE-031 is a soluble copy of the ActRIIB receptor that circulates for 10 to 14 days and catches myostatin, activins, BMP9 and BMP10 alike.
The target. Myostatin, also called GDF-8, limits how much muscle you build. It is a negative regulator, and animals and people lacking it are more muscular. Blocking it should allow more growth, and that logic is sound and well supported in animals.
Follistatin's approach. It is a natural glycoprotein that wraps around myostatin and holds it inactive before it reaches any receptor. Because it acts on the ligand instead of the receptor, it leaves the receptor free for everything else.
It also binds activins, a related family involved in reproduction, inflammation and other processes. So it is selective relative to ACE-031, and not selective in absolute terms, and nobody has measured what activin suppression does in a person over time.
ACE-031 sits one level down. It is the outer portion of the ActRIIB receptor fused to an antibody fragment, and the antibody part keeps it circulating for ten to fourteen days. [2] It works as a decoy, catching myostatin in the bloodstream before it can dock at a real receptor on muscle.
Why the decoy approach catches too much. A receptor is a door, and several proteins use it. ActRIIB accepts myostatin, activins, and BMP9 and BMP10. [1] BMP9 in particular maintains the stability of blood vessel walls, so blocking it produces bleeding. [5]
A decoy cannot tell which protein it is catching. That is the structural problem with the approach, and the reason the successor molecule was engineered to be choosier about what it binds. [8]
One consequence for anyone comparing the two. Follistatin's narrower reach is a genuine mechanistic argument in its favour. It is an argument, not evidence, because nobody has injected the protein into a person in a trial. [6]
Apitegromab binds the inactive precursor of myostatin, sparing BMP9, BMP10 and activin A, and met its Phase 3 endpoint in spinal muscular atrophy with no vascular effects of the sort that stopped ACE-031 reported. Bimagrumab blocks the receptor like ACE-031 and reports adverse events in 41 to 64 percent of patients.
Reading this page as "myostatin inhibition does not work" would be the wrong conclusion. The mechanism works. The problem was selectivity, and the field solved it by aiming at more precise targets.
Four approaches, arranged by how precisely each aims.
| Approach | What it binds | Off-target reach | Where it got to |
|---|---|---|---|
| ACE-031 | The receptor | Myostatin, activins, BMP9, BMP10 | Halted 2011, discontinued 2013 [4] |
| Bimagrumab | The receptor | Same family | Phase 2 in obesity, adverse events in 41 to 64 percent of patients [11] |
| Follistatin | Active myostatin and activins | Activins | Never tested by injection [6] |
| Apitegromab | Latent and pro-myostatin only | Spares activin A, BMP9, BMP10, TGF-beta | Phase 3 success; FDA approved 2026 [10] |
The contrast matters, but it is not a head-to-head trial. The two compounds targeting activin type II receptors have broader effects and reported tolerability concerns. The compound that binds the inactive precursor catches only myostatin, and it is the one that reached approval for spinal muscular atrophy.
Apitegromab's result is worth stating properly. SAPPHIRE enrolled 188 patients with spinal muscular atrophy, aged 2 to 21, all already on an approved treatment. At 52 weeks the 10 mg/kg group improved by 1.8 points on the Hammersmith motor function scale against placebo, and 34.2 percent achieved a three point or greater improvement against 13.5 percent on placebo. [10]
After a 2025 Complete Response Letter related to a third-party fill-finish facility, the FDA approved it as Isembyld on September 11, 2026. [10]
Bimagrumab makes the counterpoint. It targets the activin type II receptors, the same broad approach as ACE-031, and its obesity results are striking: combined with semaglutide it produced 17.8 kilograms of weight loss at 48 weeks against 14.2 on semaglutide alone, with far less lean mass lost. [11]
Its adverse event rate across trials runs between 41 and 64 percent. Blocking the receptor still costs something.
What that means for the two compounds on this page. ACE-031 is the cautionary version of an approach that has since been superseded. Follistatin sits on the correct side of the selectivity question, binding the hormone rather than the receptor, and it has still never been injected into a person in a trial. Being on the right side of an argument is not the same as having evidence.
ACE-031 has Phase 1 and Phase 2 data and a documented reason it was stopped. Follistatin has small gene therapy studies and has never been injected in a trial. Both are prohibited in sport under section S4.3.
Shared: both target myostatin · both are proteins rather than small peptides · neither Follistatin nor ACE-031 is approved anywhere · both are sold as research chemicals · neither has been tested by injection for muscle building in healthy people
| Level of action | The hormone |
| Off-target reach | Activins |
| Human evidence | Gene therapy, six patients |
| Injected form tested | No |
| Muscle effect in humans | Unestablished |
| Known safety signal | None, because none has been looked for |
| Why it is not a drug | Never developed as an injectable |
| Sold as | Recombinant protein and fragments |
| Level of action | The receptor |
| Off-target reach | BMP9 and BMP10 |
| Human evidence | Phase 1 and Phase 2 |
| Injected form tested | Yes |
| Muscle effect in humans | Demonstrated, 3.3% mean lean-mass increase at the highest dose |
| Known safety signal | Nosebleeds, gum bleeding, telangiectasia |
| Why it is not a drug | Discontinued after those events |
| Sold as | Products of uncertain identity; tested samples differed from the trial molecule |
Summary compiled from published trials, trial registry records and company announcements.
No human trial of injected follistatin protein was located. Nobody has established what products sold as ACE-031 contain, and a published analysis found 14 black-market samples did not contain a confirmed ActRIIB-Fc fusion. And neither has been tested in healthy people for muscle building.
The 2015 Becker study delivered the gene by viral vector, a different intervention with different pharmacology. [6] Every claim made for injected follistatin is extrapolation from animals and from small gene therapy studies, not injected-protein trials.
The mechanistic argument is reasonable: bind the hormone and you leave BMP9 alone. It has not been tested, and activin suppression carries its own unexamined questions.
ACE-031 as tested is a large fusion protein produced in mammalian cell culture. An analysis of 14 black-market products found none confirmed as the ActRIIB-Fc fusion tested in trials. [7]
ACE-031 caused nosebleeds, gum bleeding and telangiectasias, all resolving on discontinuation, traced to blocking BMP9 alongside myostatin. Injected follistatin protein has no human safety data located; gene-delivery studies are a different route.
These are the events that terminated a trial in children, not theoretical concerns.
This is understood, which is unusual for a halted programme.
ActRIIB is shared by myostatin, activins, BMP9 and BMP10 [1]
BMP9 maintains blood vessel wall stability [5]
Loss-of-function BMP9 mutations cause a human bleeding and vascular disorder [5]
Increased bleeding risk would plausibly compound with anticoagulants, antiplatelets or NSAIDs
Nobody has run these studies. That is different from a clean result.
The ACE-031 safety picture is unusually well characterised for a discontinued compound, and that is worth valuing rather than dismissing. The events were specific, they were reproduced across trials, the mechanism explaining them was confirmed by independent genetic work, and the sponsor ran two more years of toxicology before giving up. [3][4][5]
Follistatin has none of that, in either direction. Its safety record is not clean. It is absent.
Where this page says nothing is established, that means nobody has studied it, not that a compound is safe.
Section S4.3 of the 2026 Prohibited List names myostatin inhibitors, activin receptor IIB antagonists and myostatin-binding proteins. Both compounds are covered and both are prohibited at all times.
Section S4.3 of the 2026 Prohibited List covers agents preventing activin receptor IIB activation, and names myostatin inhibitors explicitly, including myostatin-binding proteins and agents reducing or ablating myostatin expression. [9]
Both compounds on this page are covered. ACE-031 is an activin receptor IIB antagonist by design, and follistatin is a myostatin-binding protein.
Both are prohibited at all times, in and out of competition.
Myostatin inhibitors have been a named anti-doping target since before either compound reached the market, because the muscle effect is exactly what the rules exist to prevent.
Neither Follistatin nor ACE-031 is approved anywhere. Acceleron and Shire formally discontinued ACE-031 on 2 May 2013 after two further years of toxicology work. Follistatin has never been submitted for approval as an injectable drug.
ACE-031 is not approved anywhere and its development was formally discontinued. Acceleron Pharma and Shire halted the trials in early 2011 and announced on 2 May 2013 that they had concluded their collaboration and would not restart the programme. The molecule was subsequently renamed ramatercept and shelved. [4]
That matters more than an ordinary absence of approval. A sponsor with the data, the resources and a working mechanism looked at the safety findings and chose to stop.
Follistatin has never been submitted for approval as an injectable drug. Its human work includes gene therapy studies under a research protocol. [6] There is no approved product and no application pending.
Compounding is not FDA approval. This page does not establish a blanket legal status for every pharmacy route; no FDA-approved injectable follistatin or ACE-031 product exists.
One point is specific to ACE-031. The tested molecule is a large fusion protein, the extracellular domain of a receptor joined to an antibody fragment, produced in mammalian cell culture. A published analysis of 14 black-market products found none confirmed as the same Fc fusion used in the trials. [7] Do not assume a vendor label identifies what is inside a vial.
The successor is approved. Sotatercept, marketed as Winrevair, came out of the same programme after re-engineering to avoid the off-target binding. It is approved for pulmonary arterial hypertension, not for muscle. [8]
Because trial participants developed nosebleeds, bleeding gums and telangiectasias, small dilated blood vessels in the skin. The trials were halted in early 2011 and the programme was formally discontinued in May 2013 after two further years of toxicology work.[3][4] It was not stopped for lack of effect.
Yes. A Phase 1 trial in 48 healthy postmenopausal women found a 3.3% increase in mean total-body lean mass and a 5.1% increase in thigh muscle volume at day 29 in the highest-dose group compared with placebo.[2] The muscle effect is one of the better-documented results in this category.
Nobody knows, and the mechanistic argument favours it. Follistatin binds myostatin directly and leaves the ActRIIB receptor free, so it should not block BMP9. That is what caused ACE-031's bleeding.[1][5] Nobody has injected follistatin protein into a person in a trial, so no safety data exists to check that against.[6]
Once, and not as an injection. Mendell and colleagues delivered the follistatin gene by viral vector to six patients with Becker muscular dystrophy in an open-label study.[6] Gene therapy and injecting a protein are different interventions, and the injected form has no human data.
Do not assume so. A published analysis of 14 black-market products found 12 contained full-length activin receptor IIB instead of the tested Fc fusion; two did not show the expected receptor signal.[7] In one published analysis, none of the 14 products tested was confirmed to contain the trial molecule.
No. ACE-031 failed, and the approach that replaced it worked. Apitegromab binds the inactive precursor of myostatin instead of the receptor, which leaves BMP9, BMP10 and activin A untouched, and it met its Phase 3 endpoint in spinal muscular atrophy.[10] Blocking the shared receptor was the problem, not blocking myostatin.
Apitegromab has by far the strongest evidence, with a positive Phase 3 in spinal muscular atrophy and FDA approval for that condition in 2026.[10] It is an intravenous antibody given in a clinic, not something sold as a research chemical. Bimagrumab has striking obesity results alongside semaglutide and adverse events in 41 to 64 percent of patients.[11] Neither is follistatin or ACE-031.
Not established in humans. The animal data is robust and a human study delivered the gene by viral vector to six patients, a different intervention from injecting the protein.[6] No human pharmacokinetic or efficacy data exists for injected follistatin.
It is the 344 amino acid isoform of follistatin, and the one most commonly sold. A human gene therapy study used FS-344 as the delivered gene, not as an injected protein.[6] The isoform names describe length, and none of the isoforms has been tested as an injection in a person.
Yes, both. Section S4.3 of the 2026 Prohibited List names myostatin inhibitors, including activin receptor IIB antagonists and myostatin-binding proteins, prohibited at all times.[9]
It re-engineered the molecule to stop it binding BMP9 and BMP10, and that successor is approved as Winrevair for pulmonary arterial hypertension.[8] The failure produced an approved drug, in a different disease.
What Europe PMC and ClinicalTrials.gov hold for each, on the same rule.
Follistatin has 515 records to ACE-031's 17. 169 original human studies against 10. Follistatin has 15 registered trials to ACE-031's 4.
Follistatin: WADA: Prohibited at all times, in and out of competition. S4.3 Myostatin-binding proteins (e.g. follistatin, myostatin propeptide). Non-Specified.
ACE-031: WADA: Prohibited at all times, in and out of competition. S4.3 Agents preventing activin receptor IIB activation: decoy activin receptors (e.g. ACE-031). Non-Specified.
The published recordFollistatin
Papers and trials about Follistatin
257 papers tagged human · 169 not reviews or lab · 16 clinical trial publications
15 registered trials · 1 with posted results
Compare this against the whole library →
Prohibited at all times, in and out of competition. S4.3 Myostatin-binding proteins (e.g. follistatin, myostatin propeptide). Non-Specified.RegulatorsCounted from Europe PMC indexing, not read by a person; a human tag can land on reviews, commentary or lab papers; clinical trial publications is the narrower count. 500 papers and 15 trials indexed in detail.
The published recordACE-031
Papers and trials about ACE-031
14 papers tagged human · 10 not reviews or lab · 2 clinical trial publications
4 registered trials · 1 with posted results
Compare this against the whole library →
Prohibited at all times, in and out of competition. S4.3 Agents preventing activin receptor IIB activation: decoy activin receptors (e.g. ACE-031). Non-Specified.RegulatorsCounted from Europe PMC indexing, not read by a person; a human tag can land on reviews, commentary or lab papers; clinical trial publications is the narrower count.
ActRIIB ligand-trap receptor biology and BMP9/10 binding. See ACE-031 clinical trial and BMP9 vascular genetics.
Attie KM et al. A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers. Muscle Nerve. 2013. PMID 23169607. At day 29 the highest-dose group had 3.3% higher mean total-body lean mass and 5.1% higher thigh muscle volume, both P=0.03; 48 participants.
Campbell C et al. Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy. Muscle Nerve. 2017;55:458–464. PMID 27462804. NCT01099761; extension NCT01239758.
Acceleron and Shire ended their ACE-031 collaboration May 2, 2013. ClinicalTrials.gov programme record.
Wooderchak-Donahue WL et al. BMP9 mutations cause a vascular-anomaly syndrome with phenotypic overlap with hereditary hemorrhagic telangiectasia. Am J Hum Genet. 2013;93:530–537. PubMed search.
Mendell JR et al. A phase 1/2a follistatin gene therapy trial for Becker muscular dystrophy. Molecular Therapy. 2015;23(1). Six participants received AAV1.CMV.FS344 gene delivery by intramuscular injection, not follistatin protein. PMID 25322757. A second six-person AAV study in inclusion body myositis was published in 2017: PMID 28279643.
Gel Electrophoretic Detection of Black Market ACE-031. Drug Testing and Analysis. 2025. PMID 40312924. In 14 tested products, 12 contained full-length activin receptor IIB instead of the studied Fc fusion; the other two lacked the expected receptor signal. This does not establish the contents of every vendor's product.
FDA. WINREVAIR (sotatercept-csrk) approval label. Approved for pulmonary arterial hypertension in 2024, not muscle growth.
World Anti-Doping Agency. 2026 Prohibited List, section S4.3 (agents preventing activin receptor IIB activation / myostatin inhibitors). Check the latest list for future updates.
SAPPHIRE, NCT05156320. The FDA approved apitegromab-mstn (Isembyld) for spinal muscular atrophy on September 11, 2026. Muscular Dystrophy Association announcement.
Bimagrumab obesity studies and combined semaglutide treatment. ClinicalTrials.gov search. Cross-study adverse-event percentages are not interchangeable with ACE-031 trial rates.