Follistatin is a glycoprotein encoded by the FST gene. For Minicircle, its most interesting property is that it suppresses myostatin, a protein that inhibits muscle growth. The absence of myostatin means muscle cells can replicate and grow without the usual biological controls. 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-building effect.
Researchers have tried to harness this pathway to treat neuromuscular disorders that involve weak or underdeveloped muscles, such as ALS and muscular dystrophy. Success has been limited: “So far, nothing has been shown to be as effective in human clinical trials as in animal models,” says Scott Harper, principal investigator at the Center for Gene Therapy at Nationwide Children’s Hospital. Ohio. Even so, Minicircle’s work to continue these efforts isn’t too unorthodox.
Where the plans stray from the established literature and approach wellness quackery is that the startup aims to use follistatin gene therapy to improve muscle and overall wellness in healthy participants as well. . Minicircle’s Mirror advertisement for the trial portrays the therapy as a kind of anti-aging, muscle-pumping elixir – something much less well supported by the existing evidence.
“Follistatin gene therapy increases muscle mass in animals. It doubles bone density and halves body fat, the cardiovascular system improves rapidly, the animals live longer and they are healthier,” Davis said. In fact, his ad hoc human experiments and those of his associates with follistatin are what provided the impetus for starting Minicircle: “We’ve seen some very interesting effects,” he said.
But Harper says he hasn’t heard anything about Minicircle’s more outlandish claims that follistatin gene therapy decreases chronic inflammation and body fat, boosts DNA repair and promotes liver reversal. ‘age. 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 are also critical of the company’s namesake minicircle technology. This approach includes a non-viral delivery method using a circular genetic construct – a “minicircle” – to transport genetic material into target cells.
But human studies using the minicircle technique have so far failed to deliver DNA to the cell nucleus in a clinically relevant, safe and therapeutic way, says one of its creators, Mark Kay. , a professor of genetics at Stanford University (although he notes that the method has had some success in vaccines). From what he was able to discover 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 technologies?” he asks. “How is it different? »
Minicircle’s approach departs from the main focus of the broader field of gene therapy: the use of viral vector technology, where a neutralized virus delivers the new genetic material to target cells. However, Kotin notes that the non-viral vector approach, like the one used by Minicircle, is much simpler and cheaper to produce – and less likely to induce certain adverse events, like lethal shocks to the immune system. The company’s reversibility claim appears to be based on the idea that minicircles, unlike viruses, can be administered more than once, he says. (Of course, whether Minicircle’s treatments will work, reversibly or not, remains to be seen.)
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