Follistatin
Follistatin is an endogenous activin-binding glycoprotein that antagonises myostatin (GDF-8) and activins, and it has been studied as a way to increase muscle mass in muscle-wasting diseases. Human experience is limited to early-phase gene-therapy trials (for example, AAV-delivered follistatin for Becker muscular dystrophy and inclusion body myositis); no follistatin product is approved for any indication.
Mechanism
In plain terms, follistatin removes a natural stop signal that limits how much muscle can grow. Technically, it is a high-affinity binding protein that sequesters myostatin and activin, preventing them from activating activin type II receptors (ActRIIB) and the downstream Smad2/3 signalling that restrains muscle. By neutralising these ligands, follistatin permits increased muscle fibre growth in animal models, which is the rationale for follistatin gene therapy in muscular dystrophies. Human efficacy and long-term safety remain unestablished.
Regulatory Status by Region
- United States (FDA)Not approved for any indication; follistatin-based gene therapies have been studied only in early-phase clinical trials.
- Australia (TGA)Not on the Australian Register of Therapeutic Goods (ARTG); an unapproved substance with no registered therapeutic product.
- European Union (EMA)No EMA marketing authorisation; not an approved medicine in the EU.
- WADAProhibited at all times under Section S4.3 (Agents preventing activin receptor IIB activation), which explicitly names follistatin among myostatin-binding proteins; gene-therapy delivery may additionally be captured under M3 (Gene and Cell Doping).
Key Studies
- Regulation of myostatin activity and muscle growth (demonstrating that follistatin overexpression blocks myostatin and increases muscle mass) (Lee SJ, McPherron AC. Proc Natl Acad Sci U S A. 2001.)
- A phase 1/2a follistatin gene therapy trial for Becker muscular dystrophy (Mendell JR, et al. Mol Ther. 2015.)
Related Clinical Trials
- CALM-AF-AI: Counteracting Age-related Loss of Muscle With AAV-Follistatin Combined With Angiogenesis-Inducing VEGF Plasmid Gene TherapyPhase 1/Phase 2 · Recruiting
- Refining Fertility-sparing Treatment in Endometrial Carcinoma Based on Molecular ClassificationPhase 2/Phase 3 · Recruiting
- Safety and Efficacy of Klotho and Follistatin Gene TherapyEARLY_Phase 1 · Recruiting
- Effect of Acute Endurance Exercise on the Production of FGF21 and Follistatin in Patients With Hepatocellular CarcinomaN/A · Not Yet Recruiting
- The Regulatory Role of miRNA 27 Follistatin Like Protein-1 Gene in Multiple ScelerosisN/A · Unknown
- Evaluation of Serum Follistatin-Like Protein 1 Levels in Behcet's Disease and Its Association With Disease ActivityN/A · Completed
- Phase I: Safety and Efficacy of an Injectable Follistatin Plasmid Gene Therapy in HumansPhase 1 · Completed
- Follistatin Levels in Metabolically Healthy and Unhealthy Obese IndividualsN/A · Completed