Follistatin-344
From PeptidePlaza, the free peptide reference · Entry #042 · Recovery · Hand-curated entry · Editorial standards
Follistatin-344 (also known as FS-344, FST-344, Follistatin) is a recovery research peptide. A glycoprotein that binds and neutralises myostatin — the brake on muscle growth. Knock out the brake in animals and muscle mass increases dramatically.
Follistatin is an endogenous single-chain glycoprotein that binds members of the TGF-β superfamily — most notably myostatin (GDF-8) and activin A — and prevents them from engaging their receptors. Myostatin is the principal negative regulator of skeletal muscle mass: animals and humans with loss-of-function myostatin mutations display dramatic muscular hypertrophy. Follistatin-344 refers to the 344-amino-acid isoform (FST-344), the precursor form that gives rise to the circulating FST-315 variant. In transgenic and viral gene-transfer studies, follistatin overexpression produces large increases in muscle mass and strength in mice and non-human primates, and AAV-delivered FS-344 has been trialled in Becker muscular dystrophy and sporadic inclusion body myositis with modest functional gains. Follistatin also plays roles in FSH regulation, inflammation and fibrosis. As a research compound sold in vial form it is problematic: it is a large glycoprotein rather than a synthetic peptide, its systemic half-life is very short, and correct glycosylation — required for full activity — is not achievable by standard peptide synthesis. Most of the compelling data comes from gene therapy delivering sustained local expression, not from injecting recombinant protein.
1 Mechanism of action
Binds myostatin (GDF-8), activin A, GDF-11 and related TGF-β superfamily ligands with high affinity, preventing receptor engagement and downstream SMAD2/3 signalling. Removing myostatin's inhibitory tone permits satellite cell proliferation, increased protein synthesis and muscle fibre hypertrophy.
Primary targets: Myostatin (GDF-8) — ligand trap · Activin A · GDF-11 · ActRIIB signalling axis (indirect)
2 Reported effects
Effects below are those reported in the published literature cited on this page. They are not claims of clinical benefit and not medical advice.
2.1 Reported benefits
- Potent neutralisation of myostatin, the primary negative regulator of muscle mass
- Large increases in muscle mass in transgenic and gene-transfer animal models
- Functional improvement in early gene therapy trials for muscular dystrophy and IBM
- Also antagonises activin A and GDF-11, with anti-fibrotic effects in some models
- Relevant to sarcopenia and cachexia research
2.2 Side effects
- Effectively no human safety data for injected recombinant protein
- Immunogenicity risk — a large foreign glycoprotein can provoke antibody responses
- Disruption of FSH regulation and reproductive endocrinology via activin blockade
- Injection site reactions
- Theoretical tumour risk from broad TGF-β superfamily antagonism
- Tendon strength may not keep pace with muscle hypertrophy
3 Chemical and physical properties
| Molar mass | ~38,000 g/mol (glycosylated) |
|---|---|
| Purity (typical) | >95% |
| Half-life | Very short systemically (minutes to ~1 hour for circulating protein) |
| Storage | −20 °C, lyophilised powder, desiccated |
| Solubility | Sterile water / bacteriostatic water |
| Receptors / targets | Myostatin (GDF-8) — ligand trap, Activin A, GDF-11, ActRIIB signalling axis (indirect) |
3.1 Amino acid sequence
344-amino-acid glycoprotein (FST-344 precursor isoform); not a synthetic peptide
4 Research dosages
No validated protocol for recombinant protein. Gene therapy trials delivered AAV1.CMV.FS344 intramuscularly at defined vector genome doses — not translatable to vial dosing.
5 Research studies (7)
- Follistatin Gene Therapy for Sporadic Inclusion Body Myositis
Molecular Therapy (2017) · Case Series · N=6AAV1.CMV.FS344 delivered intramuscularly in patients with sporadic inclusion body myositis, followed over multiple years.Key finding: Treated patients showed improved 6-minute walk distance versus untreated comparators, with no serious adverse events attributed to the vector. - Combined resistance exercise and essential amino acid intake enhance follistatin/myostatin ratio and muscle fitness in older women: a randomized controlled trial.
Journal of the International Society of Sports Nutrition (2026) · RCTA 12-week intervention combining resistance exercise and essential amino acid supplementation was superior to either intervention alone in enhancing muscle mass, muscle fitness, myokine profiles, and reducing... - The impact of weight loss on fat-free mass, muscle, bone and hematopoiesis health: Implications for emerging pharmacotherapies aiming at fat reduction and lean mass preservation.
Metabolism: clinical and experimental (2024) · ReviewSimilar to bariatric surgery, incretin receptor agonists have revolutionized the treatment of obesity, achieving up to 15-25 % weight loss in many patients, i.e., at a rate approaching that achieved with... - A molecular pathway for cancer cachexia-induced muscle atrophy revealed at single-nucleus resolution.
Cell reports (2024) · PreclinicalCancer cachexia is a prevalent and often fatal wasting condition that cannot be fully reversed with nutritional interventions. - Safe and effective in vivo delivery of DNA and RNA using proteolipid vehicles.
Cell (2024) · PreclinicalGenetic medicines show promise for treating various diseases, yet clinical success has been limited by tolerability, scalability, and immunogenicity issues of current delivery platforms. - Serum and Pulmonary Expression Profiles of the Activin Signaling System in Pulmonary Arterial Hypertension.
Circulation (2023) · PreclinicalThese findings offer new insights into the activin signaling system in PAH and show that activin A and FSTL3 are prognostic biomarkers for PAH. - Myostatin and follistatin as monitoring and prognostic biomarkers in dysferlinopathy.
Neuromuscular disorders : NMD (2023) · PreclinicalMyostatin is a myokine which acts upon skeletal muscle to inhibit growth and regeneration.
6 Safety and risk profile
6.1 Regulatory status
Follistatin-344 is currently classified as Investigational. It has no approved human indication in the United States; availability elsewhere does not imply demonstrated safety or efficacy.
Safety score: 40/100 — moderate concern. Derived from clinical data volume, known risks and regulatory status.
6.2 Contraindications
Conditions and populations in which use is contraindicated:
- Known or suspected malignancy
- Pregnancy or lactation
- Reproductive endocrine disorders (activin/FSH axis interference)
- History of significant immunogenic drug reactions
6.3 Drug interactions
| Drug or class | Interaction | Risk |
|---|---|---|
| Anabolic androgenic steroids / SARMs | Additive hypertrophic signalling with compounded tendon and cardiac loading risk; no safety data. | High |
| Fertility treatments (FSH, gonadotropins) | Activin antagonism directly interferes with FSH regulation. | High |
| Growth hormone secretagogues | Complementary anabolic pathways; entirely uncharacterised in combination. | Moderate |
6.4 Long-term risks
- Unknown consequences of chronic myostatin and activin blockade
- Theoretical malignancy risk from TGF-β superfamily interference
- Musculotendinous imbalance if muscle mass outpaces connective tissue adaptation
- Antibody formation neutralising endogenous follistatin
6.5 Research best practices
- Store lyophilised at −80 °C where possible; −20 °C minimum, strictly desiccated
- Avoid all freeze-thaw cycles — large glycoproteins denature readily
- Verify identity by SDS-PAGE or mass spec; HPLC purity alone is inadequate for a glycoprotein
- Treat vendor claims of "follistatin peptide" with scepticism — the active molecule is a protein
7 Frequently asked questions
- Does injecting follistatin build muscle?
- The strong data comes from gene therapy producing sustained local expression, not from injecting recombinant protein. Circulating follistatin is cleared within minutes and is a glycoprotein whose activity depends on correct glycosylation — something research-grade material often lacks. Extrapolating from AAV gene transfer results to a subcutaneous vial is not justified.
- Why is myostatin inhibition attractive?
- Myostatin is the dominant brake on muscle growth. Natural loss-of-function mutations in cattle, dogs and a documented human case produce extreme muscularity, making the pathway an obvious target for muscle-wasting disease. Multiple pharmaceutical programmes have pursued it — most have failed on efficacy or safety in humans.
- What are the safety concerns?
- Follistatin blocks activin and GDF-11 as well as myostatin, so effects are not confined to muscle. Activin signalling regulates FSH, inflammation, fibrosis and tissue homeostasis; broad neutralisation has unknown long-term consequences, including theoretical tumour-related risks given the TGF-β superfamily's role in growth control.
8 References
- Combined resistance exercise and essential amino acid intake enhance follistatin/myostatin ratio and muscle fitness in older women: a randomized controlled trial. PubMed (2026). Jeong D, et al.. View source
- The impact of weight loss on fat-free mass, muscle, bone and hematopoiesis health: Implications for emerging pharmacotherapies aiming at fat reduction and lean mass preservation. PubMed (2024). Stefanakis K, et al.. View source
- A molecular pathway for cancer cachexia-induced muscle atrophy revealed at single-nucleus resolution. PubMed (2024). Zhang Y, et al.. View source
- Safe and effective in vivo delivery of DNA and RNA using proteolipid vehicles. PubMed (2024). Brown DW, et al.. View source
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