Follistatin

Follistatin is a naturally occurring glycoprotein that functions as a potent inhibitor of myostatin and other members of the transforming growth factor-beta (TGF-β) superfamily including activins. By neutralizing myostatin—the primary negative regulator of skeletal muscle growth—follistatin effectively removes the biological brake on muscle development. Research demonstrates that follistatin overexpression or administration leads to significant increases in muscle mass and strength in animal models. The protein also influences reproductive physiology, inflammation, and metabolic processes through its effects on activins. Different follistatin isoforms (FS288, FS303, FS315) have varying tissue distributions and binding characteristics. Gene therapy approaches using follistatin have entered clinical trials for muscular dystrophies, showing improved muscle function and ambulation. Research continues exploring follistatin's potential for muscle wasting conditions, sarcopenia, and age-related muscle loss. The protein's effects extend beyond muscle to include roles in wound healing and fibrosis modulation.

The only human evidence is from small, open-label, non-randomized gene-therapy trials in rare muscle diseases; effects were variable and no randomized placebo-controlled trial exists. There is no evidence supporting follistatin peptide injections for muscle gain in healthy people. WADA bans follistatin in sport.

Follistatin is a naturally occurring glycoprotein that binds and neutralizes myostatin and activins (TGF-beta superfamily). In clinical gene-therapy trials, the FS344 isoform was delivered via AAV1 by direct intramuscular injection into the quadriceps (dose 3x10^11 vg/kg/leg in cohort 1). The peptide itself has a short plasma half-life, which is why trials used gene delivery rather than peptide injections.