Follistatin-344: mechanism, research and approval status
Clinical review pending
What follistatin-344 is proposed to do, what small gene-therapy studies show, and why they do not establish the efficacy or safety of the injectable peptide being sold.
Is follistatin-344 effective and safe for building muscle in humans? Neither has been established for the peptide sold as an injection. Small gene-therapy studies in people with muscle diseases offer early findings. Those results cannot, however, be applied to the injectable product or to use in healthy people.
What is follistatin-344?
Follistatin is a protein naturally produced by the body. It binds myostatin and related factors, neutralizing their effects. Follistatin-344 (FS344) refers to a particular form containing 344 amino acids that researchers use, among other things, to develop gene therapies.
The market for performance-enhancing substances also offers an injectable “follistatin peptide” for muscle building. This incompletely characterized product differs from the material used in gene therapy. It is not an approved medicine.
How does it work?
Myostatin normally limits the growth of muscle mass. By binding and neutralizing myostatin, follistatin is intended to weaken this constraint and allow more muscle growth. This pathway is well established in animal models [1]: disrupting myostatin signaling produces substantially greater muscle growth. That explains the proposed mechanism. Animal experiments do not establish whether people can achieve comparable results by injecting the peptide being sold.
Is it FDA-approved?
No. The US Food and Drug Administration has not approved follistatin-344 as a medicine. Several different uses need to be distinguished:
- The injectable peptide is categorized as a research chemical and performance-enhancing substance. It has no recognized status within the US “compounding” system, in which medicines are individually prepared on prescription.
- The gene therapy remains under investigation in clinical trials.
- In sport, the WADA Prohibited List bans myostatin-binding proteins, including follistatin, at all times.
What does the research show?
The human studies described here investigated a gene therapy. In a small phase 1/2a trial [2], six patients with Becker muscular dystrophy received a treatment that transferred the follistatin gene (FS344). Walking ability improved in some patients, and researchers also observed changes in muscle tissue. A follow-up report [3] provided further walking data.
These findings do not establish a benefit for the injectable follistatin peptide marketed as a wellness product: both the treatment and the patient population differ from peptide injections in healthy people. Its efficacy and safety therefore remain unestablished. No controlled human studies of this injectable peptide are cited here.
Two small studies with different comparison conditions examined changes in walking ability following gene therapy:
| Study | Patients | Study design | Result |
|---|---|---|---|
| Phase 1/2a trial in Becker muscular dystrophy | 6 treated patients | No placebo group | 4 of the 6 patients covered a greater distance in the six-minute walk test, walking 29 m to 125 m farther [4]. Muscle biopsies showed less fibrosis, meaning less replacement of muscle tissue with connective tissue. |
| Study in sporadic inclusion body myositis [5], an inflammatory muscle disease, published in 2017 | 6 treated patients compared with 8 untreated controls selected for matching characteristics | The same gene therapy combined with an exercise program; no random allocation to the control group | In treated patients, six-minute walk distance increased by a median of 56.0 m per year. In the control group, it fell by 25.8 m (p = 0.01). Individual changes among treated patients ranged from 5 to 153 m. |
The 2017 study involved only a few patients, and treatment and control groups were not formed through random assignment. The observed improvement in walking ability provides a reason to investigate the gene therapy further. This study does not provide robust evidence of its efficacy.