Follistatin-344: Myostatin and Activin-Binding Protein
Splice variant of the follistatin gene that binds and neutralises myostatin and activins. Pre-clinical muscle growth effects; no human approval.
🐀 Animal
- Full name
- Follistatin-344 (FST-344)
- Class
- Myostatin/activin-binding glycoprotein splice variant
- Half-life
- Minutes (native); AAV gene-therapy approaches studied
- Route
- Research: intramuscular / AAV vector
- Developer
- Academic
- Regulatory status
- No approval; WADA-banned
What it is
Follistatin is a naturally occurring protein that binds and sequesters members of the TGF-β superfamily, most notably myostatin (muscle growth inhibitor) and activins. The FST-344 splice isoform is secreted and circulates; FST-288 is the membrane-bound form. Neutralising myostatin removes a brake on muscle mass.
How it works
Myostatin normally signals through ActRIIB to limit muscle fibre size and number. Follistatin binds free myostatin and prevents receptor engagement, permitting satellite-cell activation and hypertrophy.
Activin A and B are similarly sequestered. Because activins also affect reproductive and pituitary function, supra-physiological follistatin has pleiotropic effects beyond skeletal muscle.
What the research shows
Pre-clinical gene-therapy studies in rodents and dystrophic-dog models drive interest; human trials are small and early.
Kota J. et al. (2009) — AAV-follistatin in mdx mice
Kota J. et al., Sci Transl Med 2009;1:6ra15. 🐀 Animal
AAV-delivered follistatin increased muscle mass and improved function in muscular dystrophy models.
Effects persisted for months after a single AAV injection.
Limitations: Gene therapy, not peptide administration.
Mendell JR et al. (2015) — early human AAV follistatin (BMD)
Mendell J.R. et al., Mol Ther 2015;23:192–201. 👥 Human studies
6 patients with Becker muscular dystrophy received intramuscular AAV-follistatin.
Muscle biopsies showed increased fibre size and improved 6-minute walk distance at 6 months.
Limitations: Tiny population; open-label; not generalisable to healthy use.
Safety and limitations
Gene-therapy experience is limited but generally showed local tolerability. Peptide-form follistatin has very short half-life and no controlled human data. Off-target activin suppression is a theoretical reproductive-endocrine concern.
Research-chemical products labelled “follistatin-344” cannot be assumed to match the natural protein. WADA-banned.