tuneTypical Dose
AAV1.CMV.FS344, 3×10^11-6×10^11 vg/kg/leg (BMD), 6×10^11 vg/kg (sIBM)
Peptide
Follistatin-344
Follistatin-344
Evidence TierCWADA PROHIBITED
watchEffect Window
Reported early and mid-term windows from 6 months to 1 year
lockCompliance
WADA PROHIBITED
Overview
Clinical Summary
Follistatin-344 is a protein that binds myostatin and activins, influencing muscle growth signaling. It is discussed for muscle mass enhancement, but human outcomes data are minimal.
Preclinical studies suggest increased muscle mass and reduced muscle wasting through myostatin pathway inhibition. Human evidence for meaningful functional outcomes is essentially absent, and safety data are limited. Minority considerations include metabolic and reproductive effects due to activin signaling. Benefits remain speculative without controlled clinical trials and validated dosing and safety frameworks.
Follistatin-derived vector intervention intended to antagonize myostatin/activin signaling via ActRIIB-related pathways, with strongest rationale in disease-directed gene-transfer settings.
Outcomes
What This Is Expected To Influence
Primary Outcomes
- Myostatin pathway modulation
- 6-minute walk test change in diseased cohorts
Secondary Outcomes
- Quadriceps structural/biopsy signal
- Fibrosis/regeneration trends
Safety
Contraindications and Interactions
Contraindications
- Pregnancy
- Lactation
- Minors
- Active endocrine instability
- Severe retinal history
- Active fertility planning
Side effects
- Injection site reactions
- Unknown long-term effects
Interactions
- Growth pathway modifiers
- Immunosuppressive regimens affecting immune surveillance
Avoid if
- Competitive athletes
- Vision changes
- Concurrent myostatin/Activin pathway agents
- Pregnancy or lactation
Evidence
Study-level References
follistatin-344-SRC-001Clinical trial, Phase I/IIa
Sourceopen_in_newMendell JR, Sahenk Z, Malik V, et al. A phase 1/2a follistatin gene therapy trial for becker muscular dystrophy. Mol Ther. 2015;23(1):192-201. doi:10.1038/mt.2014.200. PMID:25322757.
Population: Adult males with Becker muscular dystrophy
Dose protocol: AAV1.CMV.FS344, 3×10^11 or 6×10^11 vg/kg/leg, bilateral intramuscular quadriceps, 6MWT primary endpoint
Key findings: Majority/selected responders improved 6MWT distances. Responders were variable and fibrosis-related histologic differences were reported. Safety summary reported no major adverse event signal in abstract.
Notes: Very small, non-randomized clinical cohort.
Paper content
This phase 1/2a clinical trial evaluated AAV1-delivered follistatin gene therapy in patients with Becker muscular dystrophy (BMD). Follistatin inhibits the myostatin pathway, promoting increased skeletal muscle mass. The trial demonstrated improvements in the six-minute walk test and muscle histopathology with an acceptable safety profile.
follistatin-344-SRC-002Clinical trial
Sourceopen_in_newAl-Zaidy SA, Sahenk Z, Rodino-Klapac LR, et al. Follistatin Gene Therapy Improves Ambulation in Becker Muscular Dystrophy. J Neuromuscul Dis. 2015;2(3):185-200. doi:10.3233/JND-150083. PMID:27858738.
Population: Patients with Becker muscular dystrophy
Dose protocol: AAV1.CMV.huFS344 gene therapy in Becker muscular dystrophy patients
Key findings: Reports improved ambulation in BMD patients after follistatin gene therapy. Supports mechanistic rationale for myostatin pathway inhibition in neuromuscular disease.
Notes: Companion analysis to the Mendell 2015 trial cohort. Primarily interpretive context.
Paper content
This study reports on follistatin gene therapy for Becker muscular dystrophy. Follistatin is a secretory propeptide that inhibits the myostatin pathway, resulting in increased skeletal muscle mass. The treatment improved ambulation in patients, supporting the therapeutic potential of myostatin pathway inhibition for muscular dystrophies.
follistatin-344-SRC-003Animal study
Sourceopen_in_newKota J, Handy CR, Haidet AM, et al. Follistatin gene delivery enhances muscle growth and strength in nonhuman primates. Sci Transl Med. 2009;1(6):6ra15. doi:10.1126/scitranslmed.3000112. PMID:20368179.
Population: Cynomolgus macaque monkeys
Dose protocol: AAV1-FS344 intramuscular delivery, durable expression and strength/mass endpoints
Key findings: Reported increased muscle size and strength with expression of transgene and no major organ-level toxicity signals in this preclinical setting.
Notes: Not generalizable to human supplement or peptide injection protocols.
Paper content
Intramuscular injection of AAV1-FS344 expressing a human follistatin isoform in cynomolgus macaques produced pronounced and durable increases in muscle size and strength. Long-term transgene expression did not produce abnormal changes in key organ morphology or function, supporting the safety of this approach for potential treatment of degenerative muscle disorders.
follistatin-344-SRC-004In vitro study
Sourceopen_in_newSchneyer AL, Sidis Y, Gulati A, et al. Differential antagonism of activin, myostatin and growth and differentiation factor 11 by wild-type and mutant follistatin. Endocrinology. 2008;149(9):4589-95. doi:10.1210/en.2008-0259. PMID:18535106.
Population: Cell culture-based competitive binding analyses and in vitro bioassays using follistatin mutant panels
Dose protocol: Follistatin wild-type and mutant variants in binding/bioassays
Key findings: Confirms neutralization of activin, myostatin, and GDF11 by follistatin variants and supports selectivity logic.
Notes: Mechanistic support only. No human-dose inference.
Paper content
Follistatin mutant analysis revealed that activin binding and neutralization are mediated primarily by follistatin domain 2 (FSD2), whereas myostatin binding depends more on FSD1. Domain-swapping mutants that deleted FSD2 or replaced it with an extra FSD1 created selective myostatin antagonists with vastly reduced activin antagonism, though these mutants also bound GDF11.
follistatin-344-SRC-005Regulatory policy document
Sourceopen_in_newWorld Anti-Doping Agency, Prohibited List S4 (“Hormone and metabolic modulators”), Section S4.3 (“Agents preventing activin receptor IIB activation”)
Population: Competitive sport governance context
Dose protocol: Not applicable
Key findings: Myostatin inhibitors including myostatin-binding proteins (example: follistatin) are listed as prohibited under S4.3.
Notes: Not a clinical efficacy document. Legal status context only.
Paper content
Myostatin inhibitors including myostatin-binding proteins (example: follistatin) are listed as prohibited under S4.3.
follistatin-344-SRC-006Retrospective case series
Sourceopen_in_newDag U, Caglayan M, Oncul H, Alakus MF. Central serous chorioretinopathy associated with high-dose follistatin-344: a retrospective case series. Int Ophthalmol. 2020;40(11):3155-3161. doi:10.1007/s10792-020-01501-6. PMID:32671599.
Population: Bodybuilding athletes who developed central serous chorioretinopathy (CSCR) after high-dose follistatin-344 injections
Dose protocol: Retrospective series of 11 bodybuilding athletes using subcutaneous follistatin-344 injections from non-pharmaceutical sources
Key findings: All 11 athletes developed CSCR after follistatin-344 use. Recurrence was observed in athletes who resumed injections.
Notes: Safety signal only. Causality and exact exposure quantification are limited.
Paper content
This retrospective case series describes 11 male bodybuilding athletes who developed central serous chorioretinopathy (CSCR) following high-dose subcutaneous follistatin-344 injections. In patients with a single injection history, subretinal fluid resolved completely within approximately 2.3 months. However, patients with multiple prior injections developed recurrent CSCR, suggesting that follistatin-344 should be considered a risk factor for this retinal condition.
follistatin-344-SRC-007Clinical trial (open-label)
Sourceopen_in_newMendell JR, Sahenk Z, Al-Zaidy S, et al. Follistatin Gene Therapy for Sporadic Inclusion Body Myositis Improves Functional Outcomes. Mol Ther. 2017;25(4):870-879. doi:10.1016/j.ymthe.2017.02.015. PMID:28279643.
Population: Sporadic inclusion body myositis patients, ambulatory, mild to moderate disease
Dose protocol: rAAV1.CMV.huFS344, 6×10^11 vg/kg, bilateral quadriceps, matched untreated comparison reported
Key findings: Median annualized 6MWT improved +56.0 m/year vs -25.8 m/year untreated. Treatment responders showed improvements of 58-153 m.
Notes: Small and early-phase. Not a randomized trial.
Paper content
This open-label clinical trial evaluated AAV1-delivered follistatin (FS344) gene therapy in six ambulatory patients with sporadic inclusion body myositis. Treated subjects showed a significant annualized improvement of +56.0 m/year on the 6-minute walk test compared to a decline of -25.8 m/year in matched untreated controls. Treatment effects included decreased fibrosis and improved muscle regeneration, suggesting promise for follistatin gene therapy in mild to moderately affected patients.
follistatin-344-SRC-008Anti-doping project documentation
Sourceopen_in_newWorld Anti-Doping Agency, “Detection of Follistatin-doping in urine and blood” (18B09CR, 2018) project page
Population: Regulatory and detection context
Dose protocol: Not applicable
Key findings: Confirms class context for myostatin-modifying agents, notes no approved follistatin pharmaceuticals at time of report, and documents black-market product detection concerns.
Notes: Use for policy context and quality-risk framing, not clinical effect.
Paper content
Confirms class context for myostatin-modifying agents, notes no approved follistatin pharmaceuticals at time of report, and documents black-market product detection concerns.