Experimental gene therapy prevents obesity, builds muscle, without exercise or dieting
A compelling new study, led by scientists from Washington University School of Medicine in St. Louis, has found a novel gene therapy can prevent obesity and build muscle without the need for additional exercise, in mice being fed a high-fat diet.
Follistatin, a protein expressed in almost all animal tissue, was first discovered and described in the late 1980s. Initially investigated for its role as a reproductive hormone, follistatin was subsequently found to influence a number of cellular processes, including muscle proliferation.
Prior animal studies have demonstrated gene therapies designed to amplify follistatin expression can counteract certain degenerative muscle diseases. This new research explored whether this kind of therapy could help treat osteoarthritis by increasing muscle mass and reducing metabolic inflammation linked to obesity.
“Obesity is the most common risk factor for osteoarthritis,” explains Farshid Guilak, senior investigator on the new research. “Being overweight can hinder a person’s ability to exercise and benefit fully from physical therapy.”
The study involved young mice receiving a single gene therapy treatment designed to enhance follistatin expression. The animals were fed a high-fat diet and the progression of post-joint injury osteoarthritis was observed.
Guilak describes the subsequent results as “profound,” with the animals building muscle mass without gaining additional weight, despite being fed a high-fat diet and not exercising any more than normal. The gene therapy notably mitigated cartilage degeneration, synovial inflammation, and bone remodeling linked to joint injury and osteoarthritis.
“We’ve identified here a way to use gene therapy to build muscle quickly,” says Guilak. “It had a profound effect in the mice and kept their weight in check, suggesting a similar approach may be effective against arthritis, particularly in cases of morbid obesity.”
This is not the first time follistatin gene treatment has been proposed for human therapies. It is being investigated as a potential therapy for cancer, kidney disease and cystic fibrosis. A Phase 1 human trial testing the safety of follistatin gene therapy for Becker muscular dystrophy suggested the treatment generated no adverse effects, however, efficacy at this stage is unclear.
This new research suggests follistatin gene therapy generates a number of multifactorial effects, not just influencing muscle mass but also broad metabolic activities that can somehow counter caloric intakes in high fat diets.
Guilak is realistic about how far from a human clinical treatment his team’s research currently may be, but this promising finding does point to intriguing future gene therapies in humans that could treat obesity without major dietary change, or build muscle in subjects unable to exercise.
“Something like this could take years to develop, but we’re excited about its prospects for reducing joint damage related to osteoarthritis, as well as possibly being useful in extreme cases of obesity,” concludes Guilak.
The new research was published in the journal Science Advances.
Source: Washington University School of Medicine in St. Louis
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