Also known as: FST, Follistatin-344, Follistatin-315, FS-344
Half-life: ~30 minutes (recombinant); years (AAV expression)
Last reviewed: · Published:
Follistatin is a naturally occurring glycoprotein originally isolated from ovarian follicular fluid (hence the name). Its primary biological role is to bind and neutralize members of the TGF-β superfamily, most importantly activin A, myostatin (GDF-8), and GDF-11. By sequestering these ligands away from their receptors, Follistatin removes a tonic brake on muscle growth and promotes hypertrophy. Two principal isoforms exist: Follistatin-288 (FS-288), which is membrane-bound, and Follistatin-315 (FS-315) plus the alternative-splicing variant Follistatin-344 (FS-344), which are the soluble circulating forms.
Gene-therapy approaches using AAV vectors encoding FS-344 produced dramatic muscle hypertrophy in non-human primates without the capillary leak side effects seen with ActRIIB-Fc fusion proteins (ACE-031). A landmark 2009 study by Brian Kaspar's group demonstrated sustained muscle growth and improved force production in monkeys over more than a year. Subsequent clinical trials of AAV1-Follistatin gene therapy in inclusion-body myositis and Becker muscular dystrophy patients have shown encouraging signs.
Recombinant Follistatin protein (as sold by research peptide vendors) does not replicate the durable effect of AAV gene therapy because of its short circulating half-life, but is studied at high doses in athletes' research and self-experimentation. The strength of effect from short-course recombinant protein is much less than the published gene-therapy results and the safety profile of repeated high-dose recombinant Follistatin in humans is essentially unknown.
Follistatin was first identified in 1987 by Nakao Ueno and colleagues at the Salk Institute as an activin-binding protein isolated from porcine ovarian fluid. Its myostatin-binding activity and its role in muscle hypertrophy were established through transgenic mouse studies in the early 2000s, particularly the work of Se-Jin Lee at Johns Hopkins (the same researcher who discovered myostatin). AAV-Follistatin gene therapy was developed for muscular dystrophy and has progressed through Phase 1/2 trials at Nationwide Children's Hospital and the University of Iowa.
AAV-Follistatin gene therapy has shown a clean safety profile in clinical trials to date, with adverse events typical of AAV administration rather than Follistatin itself. The safety of repeated subcutaneous recombinant Follistatin protein in humans is essentially unstudied — the bulk of safety data comes from animal models and from gene therapy rather than peptide injection. Activin signaling is involved in reproductive function, so chronic high-dose suppression has theoretical risks on fertility and the HPG axis that have not been characterized clinically.
Dose Range
100-300 mcg
Frequency
Daily (SubQ)
Duration
10-30 days per cycle
Dose Range
Single high-titer AAV infusion
Frequency
One-time
Duration
Durable expression (years)
Dosing information is for educational purposes only. Consult a healthcare professional before using any peptide.
Typical Vial Size
1 mg
Water Type
Bacteriostatic water (BAC water)
Mixing Volume
1 mL
Half-Life
~30 minutes (recombinant); years (AAV expression)
Molecular Weight
~34-39 kDa
Reconstitute gently to preserve the glycoprotein structure. Store reconstituted vial refrigerated at 2-8°C. Use within 7-10 days as the protein is less stable than small peptides.
FDA Status
Not FDA approved as recombinant protein. AAV-Follistatin gene therapy in clinical trials.
Legal Status
Unregulated research chemical. Prohibited by WADA.
USA
Not approvedAAV gene therapy in Phase 1/2 trials
EU
Not approvedNot authorized as medicinal product
UK
Not approvedClassified as research chemical
Australia
Not approvedTGA has not authorized
Canada
Not approvedNot authorized for human use
Kota J, Handy CR, Haidet AM, Montgomery CL, Eagle A, Rodino-Klapac LR, Tucker D, Shilling CJ, Therlfall WR, Walker CM, Weisbrode SE, Janssen PM, Clark KR, Sahenk Z, Mendell JR, Kaspar BK
Science Translational Medicine (2009)
Landmark AAV-Follistatin gene therapy study in non-human primates showing sustained muscle hypertrophy and improved force generation without off-target capillary leak.
View Study →Lee SJ, Reed LA, Davies MV, Girgenrath S, Goad ME, Tomkinson KN, Wright JF, Barker C, Ehrmantraut G, Holmstrom J, Trowell B, Gertz B, Jiang MS, Sebald SM, Matzuk M, Li E, Liang LF, Quattlebaum E, Stotish RL, Wolfman NM
Proceedings of the National Academy of Sciences (2005)
Established that combined inhibition of myostatin, activin A, and GDF-11 (as Follistatin does endogenously) produces greater muscle hypertrophy than inhibiting myostatin alone, explaining Follistatin's exceptional potency.
View Study →Mendell JR, Sahenk Z, Al-Zaidy S, Rodino-Klapac LR, Lowes LP, Alfano LN, Berry K, Miller N, Yalvac M, Dvorchik I, Moore-Clingenpeel M, Flanigan KM, Church K, Shontz K, Curry C, Lewis S, McColly M, Hogan MJ, Kaspar BK
Molecular Therapy (2015)
Phase 1/2a clinical trial of AAV1-Follistatin gene therapy in Becker muscular dystrophy patients, showing improvements in 6-minute walk distance and acceptable safety.
View Study →Soluble myostatin / activin trap — recombinant decoy of the activin IIB receptor.
Short-peptide myostatin inhibitor targeting the GDF-8 / activin RIIB pathway.
Long-acting IGF-1 analog with reduced binding-protein affinity for sustained signaling.
A locally-acting IGF-1 splice variant released by muscle in response to mechanical load.
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