Description
FST-344 is an alternatively spliced isoform of the body’s own glycoprotein follistatin (FS344). Follistatin belongs to the family of antagonists of the TGF-β superfamily: it binds with high affinity to myostatin (GDF-8), but also to activin A, activin B and related ligands, preventing them from docking onto their ActRII and ActRIIB receptors. In research, myostatin and activin act as negative regulators of skeletal muscle mass. Because FST-344 inhibits both signalling pathways at once, in a research context it addresses two brakes on muscle growth instead of just one - which sets it apart from purely selective myostatin inhibitors.
The FS344 isoform was used in research specifically because it acts predominantly on skeletal muscle tissue and shows only minimal effects on non-muscle cells. Much of the robust data comes from gene-transfer models in which FS344 was expressed in muscle via a viral vector (AAV1). There is little reliable human data on the pharmacokinetics of an injected peptide or protein form - most of the evidence rests on animal models, primate studies and a handful of gene-therapy trials. When comparing gene transfer to injected protein directly, the time course and duration therefore cannot be transferred one-to-one.
The central research findings stem mostly from preclinical and early clinical models. In animal models, follistatin overexpression produced marked gains in muscle mass, driven by both hypertrophy (larger fibers) and satellite cell activation. In studies on cynomolgus macaques, a single AAV1-FS344 dose into the quadriceps produced durable increases in muscle size and strength. In phase 1/2a gene-therapy trials in patients with Becker muscular dystrophy and sporadic inclusion body myositis, functional improvements and histological changes (less fibrosis, more regeneration) were documented. Important: these studies used gene transfer, not the injectable research form.
FST-344 is a research substance intended exclusively for research and educational purposes. In the TPD catalog you get FST-344 in 10-packs with 1mg per vial. Because the reliable evidence comes almost entirely from gene-transfer models, the data on the injectable form is thin and should be regarded as largely preclinical.
This information is for research and educational purposes only. Not medical advice.
Studies
- Long-term enhancement of skeletal muscle mass and strength by single gene administration of myostatin inhibitors - PNAS 2008: A single gene administration of myostatin inhibitors (including follistatin) increased muscle mass and strength in normal and dystrophic mouse models for more than two years - even in aged animals. Preclinical (mouse, gene transfer).
- Follistatin induces muscle hypertrophy through satellite cell proliferation and inhibition of both myostatin and activin - Am J Physiol Endocrinol Metab 2009: Shows mechanistically that follistatin hypertrophy depends both on satellite cell proliferation and on the simultaneous inhibition of myostatin AND activin. Preclinical (mouse).
- Follistatin gene delivery enhances muscle growth and strength in nonhuman primates - Sci Transl Med 2009: A single AAV1-FS344 injection into the quadriceps of cynomolgus macaques produced pronounced and durable increases in muscle size and strength with no abnormal organ changes. Preclinical (primate, gene transfer).
- A phase 1/2a follistatin gene therapy trial for Becker muscular dystrophy - Mol Ther 2014: Early clinical trial with AAV1.CMV.FS344 in six BMD patients; several subjects improved on the 6-minute walk test, with reduced fibrosis and fiber hypertrophy on histology. Clinical, gene transfer.
- Follistatin gene therapy for sporadic inclusion body myositis improves functional outcomes - Mol Ther 2017: Gene transfer of FS344 into the quadriceps improved walking distance versus untreated controls, with signs of less fibrosis and more regeneration. Clinical, gene transfer.
- Discovery of a follistatin-derived myostatin inhibitory peptide - Bioorg Med Chem Lett 2019: Highlights the N-terminal domain of follistatin as the binding site for myostatin and derives a muscle-enhancing inhibitor peptide from it. Preclinical (in vitro + mouse).
Stack Notes
- MGF complements FST-344 mechanistically: while FST-344 addresses the myostatin/activin brake, MGF (Mechano Growth Factor) is associated in research with satellite cell activation after mechanical load - two different levers on the hypertrophy pathway.
- IGF-1 LR3 is frequently discussed alongside myostatin inhibition in research stacks, since the IGF-1 signalling pathway is considered the anabolic counterpart to the catabolic activin/myostatin axis. Mechanistically complementary to the FST-344 approach.
- MK-677 (Ibutamoren) raises GH/IGF-1 levels via the ghrelin receptor axis in a research context and is an oral partner that engages a different anabolic pathway than the direct myostatin/activin blockade of FST-344.
- BPC-157 is often combined in stacks because FST-344 targets muscle mass, while BPC-157 is primarily associated in preclinical studies with tendon, ligament and connective-tissue healing - sensible when muscle building and tissue resilience are in focus in parallel.
- CJC-1295 with DAC combined with Ipamorelin (GHRH plus ghrelin mimetic) addresses the GH axis and thus a growth pathway complementary to myostatin/activin inhibition.
