Researchers at Northwestern University announced a new experimental RNA therapy that, when paired with the popular weight-loss drug semaglutide, helps mice lose more body fat while preserving lean muscle mass, according to a study published in the Proceedings of the National Academy of Sciences.
How Experimental RNA Therapy Combats GLP-1 Muscle Loss
Popular GLP-1 receptor agonists like Ozempic and Wegovy help patients shed pounds, but they also cause muscle loss. Patients often regain that lost weight as fat once they stop taking the medication. To address this limitation, Northwestern researchers tested an RNA-based approach designed to switch on the body’s calorie-burning process, known as thermogenesis. According to Dr. Joseph Bass, the study’s senior author and director of the center for diabetes and metabolism at Northwestern’s Feinberg School of Medicine, the team identified an RNA therapy that promotes thermogenesis and preserves lean muscle mass when combined with semaglutide.
Did you know? Over 1.1 million people take GLP-1s without medical approval, according to data cited alongside the Northwestern University study.
Gene-Targeting Mechanism Behind the Treatment
The RNA treatment works by blocking a specific gene called ZFP423. Ordinarily, this gene prevents white fat—the kind that stores energy—from converting into beige fat, a type that burns energy. By turning off ZFP423, the therapy enables the body to expend more calories.
In laboratory tests conducted on mice, the RNA therapy administered by itself improved blood sugar control and reduced body fat without causing any muscle loss. When researchers paired the treatment with semaglutide, the outcomes improved further. Mice receiving both treatments lost only 5.5% of their muscle mass, compared to about 10% in mice treated with semaglutide alone. The combination therapy group finished with about 4 grams of body fat, contrasted with nearly 8 grams for the semaglutide-only cohort.
Origins of the Research and Commercial Collaboration
The discovery builds on years of earlier research originating in Bass’ laboratory. Chelsea Hepler, now at the University of Michigan, previously uncovered a link between the body’s internal clock and its capacity to convert fat types. That finding expanded upon earlier research by Rana Gupta at Duke University, who originally identified ZFP423 as the gene blocking that conversion.
To engineer a therapy capable of silencing the gene, Bass’ team partnered with Ionis Pharmaceuticals, a company specializing in RNA-based drugs. Following the successful animal trials, Northwestern University filed a provisional patent on the treatment, listing Bass and study first author Anneke Thorne as inventors. The National Institutes of Health helped fund the research.
Next Steps for Human Trials
With animal testing complete, Dr. Bass stated that his research team plans to evaluate the RNA therapy in human cells.
Frequently Asked Questions
What causes muscle loss during GLP-1 treatment?
Medications like Ozempic and Wegovy reduce overall weight, which frequently includes a reduction in lean muscle mass alongside fat loss.
How does the new RNA therapy protect muscle?
The experimental RNA therapy blocks the ZFP423 gene, turning white fat into calorie-burning beige fat and helping mice preserve muscle mass while on semaglutide.
Who conducted the study?
Researchers at Northwestern University’s Feinberg School of Medicine led the study, collaborating with Ionis Pharmaceuticals and building on prior work from the University of Michigan and Duke University.
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