Follistatin 344

What it is

Chemists classify Follistatin 344 as a glycoprotein, meaning it is a natural protein carrying an attached sugar group. It works by binding to and blocking two separate signaling molecules, myostatin and activin A, both members of the same broad family of growth-regulating proteins, and each normally works like a brake holding back muscle-tissue growth. The gene that produces it in the body is cut down from a longer precursor into the shorter, circulating form.

Because injected follistatin protein is cleared from the bloodstream in roughly ninety minutes, most controlled research on it has instead delivered the gene itself using a modified virus, so that muscle tissue produces a steady supply of the protein over months rather than relying on repeated injections. This gene-based approach has been tested in monkeys and, in small early-stage trials, in people with muscle-wasting diseases.

How it is studied

The strongest evidence for follistatin's effect on muscle comes from gene-therapy studies: research in monkeys using a virus to deliver the follistatin gene directly into muscle, and small early-stage human trials doing the same in people with Becker muscular dystrophy and with a separate muscle-wasting disease called inclusion body myositis. Injecting the follistatin protein itself, rather than delivering its gene, has almost no controlled human research behind it, since the protein does not stay in the body long enough for repeated injection to have an established track record.

What studies report

• In cynomolgus macaque monkeys, injecting a follistatin gene therapy into the thigh muscle produced pronounced, lasting increases in muscle size and strength, with no abnormal changes found in other organs over the study period. [kota-2009]
• In a small early-stage trial in six people with Becker muscular dystrophy, the same gene therapy given as an injection into both thighs let most patients walk farther on a six-minute walk test months later, with the biggest improvement 125 meters at the higher amount tested, along with less scarring and larger, more normal muscle fibers on biopsy; one of three patients at each amount level showed no improvement, and no adverse effects were reported. [mendell-2015]
• In a separate small trial in six people with inclusion body myositis, a different muscle-wasting disease, the same gene therapy improved six-minute walk distance by an average of 56 meters over a year, compared with a 26-meter decline in a matched group of untreated patients, though two of the six treated patients showed only slight improvement. [mendell-2017-ibm]

What is not known

Whether repeated injection of the follistatin protein itself, as opposed to gene therapy, produces any meaningful and lasting effect on muscle tissue in people has not been established; the short time the injected protein stays in the body argues against a large effect from typical injection schedules. Long-term safety of sustained follistatin activity, including any relationship to reproductive hormone levels, has only been studied for about a year even in the gene-therapy trials, and each human trial so far has involved only six patients.

Regulatory status

Neither the natural protein nor its gene-therapy form has won United States Food and Drug Administration approval for use in people outside of clinical trials. The World Anti-Doping Agency has prohibited follistatin since 2019, placing it alongside other muscle-growth-related agents banned in competitive sport.