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Gene therapy reduces fat and builds muscle in mice

18 May 2020
Appeared in BioNews 1047

A novel gene therapy prevents obesity and builds muscle without the need for additional exercise or dieting.

Researchers at Washington University School of Medicine in St Louis discovered that a novel gene therapy in mice can build strength and muscle mass quickly, resulting in a reduction in the symptoms of osteoarthritis. In addition, the same gene therapy also prevented obesity even when the mice were fed a high-fat diet and not exercising any more than usual.

'We've identified here a way to use gene therapy to build muscle quickly,' said senior investigator Professor Farshid Guilak, who is also director of research at Shriners Hospitals for Children in St. Louis. '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.'

The team gave eight-week-old mice a single injection of the gene that makes follistatin, a protein that controls metabolism, enables muscle growth and boosts fertility. Follistatin normally blocks another protein called myostatin, which regulates muscle growth, so by using this therapy, mice were able to build significant muscle mass without gaining additional weight. Specifically, mice more than doubled their muscle mass whilst also nearly doubling their strength.

With obesity being the most common risk factor for osteoarthritis, this new research aimed to investigate whether this therapy could help treat osteoarthritis by increasing muscle mass and reducing the metabolic inflammation linked to obesity.

Despite being fed a high-fat diet, the researchers found that the treated mice had fewer metabolic problems, stronger hearts, and healthier joints with less cartilage damage and inflammatory markers than their untreated counterparts. In addition, these mice were less sensitive to pain.

However, the researchers noted that they are still far off from a human clinical treatment and longer-term studies will be needed to determine the gene therapy's safety. For example, some of the muscle growth caused by gene therapy can often be harmful, such as the thickening of the heart's wall. Still, they believe that follistatin gene therapy could be a promising approach to treating degenerative muscle diseases, including muscular dystrophy.

'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,' said Professor Guilak.

The study was published in the journal Science Advances.

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