Follistatin 344

A single intramuscular injection of AAV1 carrying the FS-344 (follistatin) isoform into the quadriceps of cynomolgus macaques produced sustained follistatin expression, significant muscle fiber hypertrophy, and increased circumference and force in the treated limb over a 15-month period. Histology and serum chemistry showed no organ toxicity or off-target effects, and the myostatin-antagonizing FS-344 splice form limited unwanted circulating follistatin and reproductive-tissue effects. These primate data established the safety and efficacy rationale that supported subsequent human gene-therapy trials.

Researchers injected a virus carrying the follistatin gene into the leg muscles of monkeys. The treated muscles grew larger and stronger and stayed that way for over a year, with no signs of harm to other organs. This animal study was the key stepping stone toward testing the same approach in people.

AAV1.CMV.FS344 was delivered by direct bilateral intramuscular quadriceps injection to six Becker muscular dystrophy patients across two dose cohorts, with follow-up to 12 months. Several patients showed improvement on the 6-minute walk test (up to ~58-125 m) and muscle biopsies demonstrated fiber hypertrophy and reduced fibrosis, without significant treatment-related adverse events. The study was a small, open-label, uncontrolled proof-of-principle trial, so efficacy conclusions are preliminary and require controlled follow-up.

Six men with Becker muscular dystrophy received injections of a follistatin gene therapy into their thigh muscles. Some walked farther afterward, and muscle samples showed larger fibers and less scarring, with no serious side effects. Because the trial was tiny and had no comparison group, the results are early and encouraging rather than definitive.

This foundational study showed that transgenic overexpression of follistatin, the myostatin propeptide, or a dominant-negative activin type IIB receptor in skeletal muscle produces dramatic muscle mass increases comparable to myostatin-null mice. Follistatin's effect was notably larger than myostatin knockout alone, indicating it neutralizes additional TGF-beta family ligands such as activins beyond myostatin. The work established follistatin as a potent extracellular antagonist capable of driving skeletal muscle hypertrophy.

Scientists showed that follistatin blocks myostatin, a protein that normally limits muscle growth, and that mice making extra follistatin grew much bigger muscles. Follistatin worked even better than simply removing myostatin, because it also blocks related growth-limiting proteins. This early research explained why follistatin is such a powerful driver of muscle growth.