Follistatin-344: what has been measured about safety

This compound has a safety-relevant measurement that almost nothing else in the catalogue has, and it is about the products rather than the molecule. An anti-doping laboratory obtained seventeen black-market products carrying this name and analysed them. Nine contained follistatin. In some of the rest it found different growth-promoting peptides instead, naming MGF and GHRP-2 [12].

The same analysis reports a second thing about the nine that did contain it. Every one of them carried a His-tag, which is a handle attached to a protein so a laboratory can purify it, along with a high degree of oligomerisation [12]. A protein still carrying its purification handle is a research reagent rather than a preparation made for administration.

The rest of this page is about attribution. There is one published adverse event count in this family and it belongs to a different molecule acting in a single named muscle. Every human trial carrying the follistatin-344 name delivered a gene rather than a protein. So this page sets out which record belongs to which intervention, and where the record for an injected follistatin protein actually stops.

What this page reports, and what it does not

We report what has been documented. We do not prescribe what should be done.

Every sentence below reports what a named source measured or searched, in what system, and what it found. Where the answer is that nobody has looked, the page says which study would have looked and names the document recording that it was not done.

This page publishes no dose, no schedule, no route instruction and no list of people who should avoid anything. A list of who should not use a compound is a directions-for-use document, and it only makes sense if the reader is going to use the thing. What replaces it is a description of the compound and its record, written about the molecule rather than about the reader.

One distinction runs through everything here and is worth fixing before the first section. Three things share this name: a gene delivered inside a virus or a plasmid, which is what every human trial used; a follistatin-based fusion protein developed as a medicine, which is a different molecule; and a recombinant protein sold online, which is what the analysis above tested. Nothing said about one of the three is a statement about another.

What has been measured

What is in the products, measured rather than assumed

A 2019 study in Drug Testing and Analysis obtained seventeen black-market products carrying the follistatin 344 name and analysed them. Nine contained follistatin. In some of the remainder the laboratory found different growth-promoting peptides, and it names MGF and GHRP-2 among them [12].

All nine positive samples carried His-tagged FS344 and a high degree of its oligomers [12]. A His-tag is a short run of histidine residues attached to a protein so it can be pulled out of a mixture during purification, and it is normally removed before a protein is used for anything else. Oligomerisation means the molecules had clumped into larger assemblies. Together those two findings describe material made to be a laboratory reagent, not material made to be given to anything.

This is a measurement about a market rather than about a molecule, and that is exactly why it belongs at the top of a safety page. A question about what follistatin does in a person is downstream of a question about whether the vial contains follistatin, and for this compound the second question has an answer that no vendor document supplies. [In-vitro] [12]

The one published adverse event count, and whose molecule it is

The Phase 1 study of the follistatin-based fusion protein ACE-083, in 58 healthy postmenopausal women, reports no serious adverse events, no dose-limiting toxicities and no discontinuations resulting from adverse events [4]. It is the only study in this family whose adverse event outcome appears in a published paper. One other record posts a table to the registry without a paper behind it, and that one is set out below.

Three things separate it from the product this page is about, and each of them on its own would be enough. It is a different molecule: a fusion protein engineered by a pharmaceutical company rather than the follistatin protein itself. It was designed to act in one named muscle where it was placed rather than to circulate, so the exposure it produced is local. And it was manufactured investigational material with a regulatory file behind it, which the analysis in the section above establishes is not what is sold.

So the honest reading is that a real safety observation exists in this family and does not describe the thing readers arrive asking about. [Human RCT] [4]

Why the gene transfer trials answer a different question

Every human study carrying the follistatin 344 name delivered a gene rather than a protein. The Becker muscular dystrophy study administered rAAV1.CMV.huFollistatin344 to muscle in 15 participants, and the registry types that intervention as a biological gene transfer in its own field [1]. The Duchenne study did the same in 3 participants [2].

A gene delivered into a muscle turns that muscle into a factory producing the protein locally and continuously. An injected protein arrives all at once, distributes according to its size and clearance, and is gone. Those are different interventions rather than two routes to the same one, and a safety question about the second is not answered by observations of the first in either direction.

One of the two posted an adverse event table and it is small enough to give whole, so it is given whole. In the Duchenne study, across its 3 participants in a single arm, the registry records no death and one serious event: a head injury from a fall, 1 of 3. All 3 had at least one non-serious event, across fifteen terms: pain in 3 of 3; bruising in 2 of 3; and pharyngitis, rhinorrhea, nasal congestion, influenza, abrasion, anxiety, behavioural changes and agitation, insomnia, gastro-oesophageal reflux, constipation, a stye, increased muscle weakness and a compression fracture, each in 1 of 3 [2].

Three participants in one arm with no comparator establishes nothing about cause, in either direction. The two musculoskeletal terms are named in that list rather than summarised out of it because the intervention was aimed at muscle, and a page that grouped them under a general heading would be choosing which row of a table its reader gets to see.

The Becker study, at 15 participants, has posted no results [1]. Two further records deliver a plasmid rather than a virus, which is gene delivery of the same kind: a completed study in 43 participants [9] and a study in 30 that was recruiting when this page was reviewed [10]. Neither has posted results. Completed gene-delivery exposure in this family is therefore 61 people across three completed records, with a fourth still enrolling, and none of it is exposure to an injected protein. [Human open-label] [1] [2]

What the three terminations record, and what they do not

All three Phase 2 trials of the fusion protein were terminated, and the registry states why in the sponsor's own words. The facioscapulohumeral muscular dystrophy study was discontinued as it did not achieve functional secondary endpoints [5], the Charcot-Marie-Tooth study records the same reason [6], and the long-term extension records that investigation was discontinued because the parent trials did not achieve their functional secondary endpoints [7].

None of those is a safety reason, and this page does not supply one. A trial stopped because a drug did not do what was hoped and a trial stopped because a drug did something unwanted are different events, and here the registry field distinguishes them explicitly.

What the three terminations do establish is where the development stopped. The programme that would have accumulated long-term human exposure to a follistatin-based protein ended at Phase 2, so no such exposure record exists for any molecule in this family.

What has not been characterised

Set out plainly, so the shape of the gap is visible rather than implied. Eight registry records carry a numbered reference on this page and they divide cleanly: four deliver a gene or a plasmid [1] [2] [9] [10] and four test a different molecule designed to act in one named muscle [4] [5] [6] [7]. Not one of the eight tests an injection of the follistatin protein of the kind that is sold, which is as far as this page's own citations reach. The main review reports a wider sweep, of fifteen records naming follistatin or ACE-083 as an intervention, and reaches the same conclusion across all fifteen; that sweep carries no numbered reference of its own in this entry, and this page rests on the eight it can cite rather than restating a figure a reader cannot check. So there is no toxicology package for the product that is sold, no acute or repeat-dose study, no genotoxicity study, no developmental and reproductive study, no carcinogenicity study, and no adverse event record of any kind attributable to it.

Long-term exposure has not been characterised for any molecule in this family. The fusion protein's trials ran to a six-month primary endpoint before all three were terminated [5] [6] [7], the gene and plasmid studies were single administrations [1] [2] [9], and nothing published follows anyone beyond that.

One further thing is unmeasured and it follows directly from the analysis at the top of this page. Nobody has characterised what a His-tagged, heavily oligomerised protein does when it is injected, because the material carrying those properties is a laboratory reagent that no study was designed around. A protein carrying a purification handle and clumped into larger assemblies is not the protein any published work measured.

Our takeThis is the one compound in the catalogue where the most useful safety fact is not about the substance. An anti-doping laboratory bought seventeen products under this name and found follistatin in nine, other growth-promoting peptides in some of the rest, and a laboratory purification tag on every positive sample. Read alongside the trial record, which belongs to a gene in a virus and to a different molecule acting in one muscle, the position is that nothing published describes what is in these vials being given to anyone.

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Frequently asked questions

References

1. Nationwide Children's Hospital. Follistatin Gene Transfer to Patients With Becker Muscular Dystrophy. Phase 1, 15 participants, completed, no posted results. Intervention rAAV1.CMV.huFollistatin344, typed BIOLOGICAL in the registry record. Read through the v2 API on 23 August 2026. ClinicalTrials.gov. 2012. NCT01519349
2. Mendell JR. Clinical Intramuscular Gene Transfer of rAAV1.CMV.huFollistatin344. Phase 1/2, 3 participants, completed, results posted. Duchenne muscular dystrophy. ClinicalTrials.gov. 2015. NCT02354781
3. Mendell JR, Sahenk Z, Malik V, Gomez AM, Flanigan KM, Lowes LP, Alfano LN, Berry K, Meadows E, Lewis S, Braun L, Shontz K, Rouhana M, Clark KR, Rosales XQ, Al-Zaidy S, Govoni A, Rodino-Klapac LR, Hogan MJ, Kaspar BK. A phase 1/2a follistatin gene therapy trial for becker muscular dystrophy. Mol Ther. 2015. PMID 25322757 Identified from PubMed metadata; the full text was not read for this page.
4. Glasser CE, Gartner MR, Wilson D, Miller B, Sherman ML, Attie KM. Locally acting ACE-083 increases muscle volume in healthy volunteers. Muscle Nerve. 2018. PMID 29486514 DOI 10.1002/mus.26113 Phase 1 in 58 healthy postmenopausal women, 42 on drug and 16 on placebo. Maximum mean muscle volume increases of 14.5 per cent and 8.9 per cent, with no significant changes in mean muscle strength, and no serious adverse events or dose-limiting toxicities. Read as an abstract.
5. Acceleron Pharma, Inc. Study of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy. Phase 2, 95 participants, terminated, results posted. The registry's whyStopped field reads: Study was discontinued as it did not achieve functional secondary endpoints. ClinicalTrials.gov. 2016. NCT02927080
6. Acceleron Pharma, Inc. Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease. Phase 2, 63 participants, terminated, results posted. The registry's whyStopped field records that investigation was discontinued as it did not achieve functional secondary endpoints in the parent trial. ClinicalTrials.gov. 2017. NCT03124459
7. Acceleron Pharma, Inc. Extension Study to Evaluate the Long-Term Effects of ACE-083. Phase 2, 62 participants, terminated, results posted. The registry records that investigation was discontinued because functional secondary endpoints were not achieved in the parent trials. ClinicalTrials.gov. 2019. NCT03943290
8. Patel K. Follistatin. Int J Biochem Cell Biol. 1998. PMID 9785474 A review of the protein and its splice forms, including the 344 and 315 residue variants.
9. Minicircle. Phase I: Safety and Efficacy of an Injectable Follistatin Plasmid. 43 participants, completed, no posted results. Intervention typed GENETIC in the registry record. This site states what the registry records and nothing about the organisation. ClinicalTrials.gov. 2024. NCT06411366
10. Minicircle. Follistatin and klotho gene therapy in healthy adults. Early Phase 1, 30 participants, recruiting as of 23 August 2026. ClinicalTrials.gov. 2026. NCT07285629
11. Rodino-Klapac LR, Haidet AM, Kota J, Handy C, Kaspar BK, Mendell JR. Inhibition of myostatin with emphasis on follistatin as a therapy for muscle disease. Muscle Nerve. 2009. PMID 19208403 Identified from PubMed metadata; the full text was not read for this page.
12. Reichel C, Gmeiner G, Thevis M. Detection of black market follistatin 344. Drug Test Anal. 2019. PMID 31758732 DOI 10.1002/dta.2741 Seventeen black-market products were analysed. Nine contained follistatin; in some of the others growth-promoting peptides including MGF and GHRP-2 were found. All nine positive samples contained His-tagged FS344 and a high degree of its oligomers. Read as an abstract, which states these figures explicitly.