Preclinical Research & Experimental

Follistatin-344

also known as: FS-344, Follistatin 344

The longer of the two principal follistatin splice variants — binds tissues less avidly than FS-315 and therefore has broader systemic distribution, making it the form used in most gene-therapy and myostatin-inhibition research.

A 344-residue splice variant of follistatin (as opposed to the 315-residue FS-315 form) that potently neutralizes myostatin (GDF-8), activin A, and several related TGF-β superfamily ligands, and which has been the vehicle for most myostatin-inhibition gene therapy programs in animal models.

Mechanism of action

Binds and inactivates myostatin (a negative regulator of muscle mass), activin A, and other TGF-β family ligands. Myostatin-null mammals — including the famous double-muscled Belgian Blue cattle and rare human mutation carriers — exhibit dramatic skeletal muscle hypertrophy, establishing the therapeutic rationale. Injected or gene-therapy-delivered follistatin phenocopies part of this effect in animal models.

Primary uses

  • Muscle wasting research (Duchenne, Becker, IBM)
  • Sarcopenia research
  • Community bodybuilding use (unapproved, typically sold as sketchy injectable preparations)

Typical dosing

research-only varies (intramuscular or subcutaneous (community))

No established human dosing for injected recombinant protein. Gene therapy dosing (AAV1 viral titers) is not comparable to peptide injection.

Regulatory status

Not approved. Acceleron/Milo Biotechnology-sponsored AAV1-follistatin gene therapy (using the FS-344 sequence) reached Phase 1/2 trials in Becker muscular dystrophy and sporadic inclusion body myositis (NCT01519349, NCT02354781) with mixed functional results. No approved product.

References

  1. [clinicaltrials] NCT01519349 — "Follistatin Gene Transfer to Patients With Becker Muscular Dystrophy and Sporadic Inclusion Body Myositis." ClinicalTrials.gov.
  2. [pubmed] Mendell JR, et al. "A phase 1/2a follistatin gene therapy trial for becker muscular dystrophy." Mol Ther, 2015;23:192-201.
  3. [pubmed] Lee SJ. "Regulation of muscle mass by myostatin." Annu Rev Cell Dev Biol, 2004;20:61-86.

Related peptides

Follistatin-315

The dominant circulating follistatin isoform in human serum — binds heparan sulfate proteoglycans avidly, concentrating at tissue surfaces rather than circulating freely, which limits its systemic reach compared to FS-344.

ACE-031

Acceleron's first-generation myostatin trap — Phase 2 development in Duchenne muscular dystrophy was halted in 2013 after epistaxis and telangiectasia adverse events, but the same scaffold concept led to successor programs at Acceleron, Regeneron, and Lilly.

PEG-MGF

A pegylated fragment of a proposed muscle-specific IGF-1 splice variant — the underlying "MGF" biology remains scientifically contested, and PEG-MGF itself has no human clinical data.

IGF-1 LR3

A 13-amino-acid N-terminal extension plus Arg3 substitution gives IGF-1 LR3 roughly 2–3× the potency of native IGF-1 in bioassays — a research-reagent favorite that became a bodybuilding staple despite no human approval.
Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.