Follistatin is a glycoprotein encoded by the FST gene. To Minicircle, its most interesting property is that it suppresses myostatin, a protein that inhibits muscle growth. Missing myostatin means muscle cells can replicate and expand without the usual biological checks. As a result, animals with mutations in this gene—like the physically imposing “bully whippet”—are loaded with cartoonishly bulging muscles. Follistatin gene therapy, in theory, offers a fast track to this muscle-boosting effect.
Researchers have tried to harness this pathway to treat neuromuscular disorders that involve weak or underdeveloped muscles, like ALS and muscular dystrophy. Success has been limited: “So far, nothing has proven to work in human clinical trials like it does in animal models,” says Scott Harper, a principal investigator at the Center for Gene Therapy at the Nationwide Children’s Hospital in Ohio. Even so, Minicircle’s work to continue these efforts isn’t too unorthodox.
Where plans veer from the established literature and into territory closer to wellness quackery is that the startup aims to use follistatin gene therapy to enhance the muscles, and general well-being, of healthy participants too. Minicircle’s Mirror advertisement for the trial pitches the therapy as a kind of age-reversing and muscle-pumping elixir—something far less well supported by existing evidence.
“The follistatin gene therapy increases muscle mass in animals. It doubles bone density and halves body fat, the cardiovascular system is rapidly improved, the animals live longer, and they’re healthier,” claimed Davis. In fact, his and his associates’ ad hoc human experiments with follistatin are what served as the impetus to start Minicircle: “We’ve seen some very interesting effects,” he said.
But Harper says he hasn’t heard anything related to Minicircle’s more outlandish claims that follistatin gene therapy decreases chronic inflammation and body fat, boosts DNA repair, and promotes age reversal. Robert Kotin, a gene therapy expert and professor of microbiology and physiological systems at the University of Massachusetts Medical School, echoes Harper’s skepticism: “If I wanted to make a fountain-of-youth drug, I don’t think it would be follistatin.”
Experts also criticize the company’s namesake minicircle technology. This approach comprises a non-viral delivery method using a circular genetic construct—a “minicircle”—to traffic genetic material into target cells.
But human studies using the minicircle technique have so far failed to deliver DNA to the nucleus of the cell in a way that is clinically relevant, safe, and therapeutic, says one of its creators, Mark Kay, a Stanford University professor of genetics (although he notes that the method has found some success in vaccines). From what he could find out on Minicircle’s website, Kay doesn’t understand why the startup would succeed where others have failed. “Where’s the novelty in any of their technology?” he asks. “How is it different?”
Minicircle’s approach diverges from the main focus of the wider gene therapy field: the use of viral vector technology, where a neutralized virus delivers the new genetic material to the target cells. However, Kotin notes that the non-viral vector approach, like the one used by Minicircle, is far simpler and cheaper to produce—and less likely to induce certain adverse events, like fatal shocks to the immune system. The company’s claim of reversibility seems to rely on the idea that minicircles, unlike viruses, can be administered more than once, he says. (Of course, whether Minicircle’s treatments will work at all—reversibly or otherwise—is yet to be determined.)