An experimental RNA-based therapy combined with semaglutide preserves lean muscle mass and promotes body fat loss better than GLP-1 medications alone, according to a new study published in the Proceedings of the National Academy of Sciences. Researchers at Northwestern University tested the treatment in mice, finding that the dual-drug approach reduced lean-muscle loss while significantly increasing overall fat reduction.
How the RNA Therapy Targets Body Fat
Popular GLP-1 medications like Wegovy and Ozempic have transformed weight-loss treatments, but patients frequently shed lean muscle mass alongside body fat. While losing some muscle is typical during major weight reduction, significant muscle loss slows metabolism, triggers fatigue, increases inflammation, and complicates long-term weight management. To combat this, researchers at Northwestern’s Feinberg School of Medicine investigated an experimental RNA strand designed to silence the ZFP423 gene.
This specific gene slows white fat’s ability to transform into energy-burning beige fat. By silencing ZFP423, the RNA treatment releases the biological brake on thermogenic energy expenditure. When tested by researchers, the therapy encouraged white fat to convert into burnable beige fat, allowing the body to target fat weight more effectively without sacrificing essential muscle integrity.
Laboratory Results in Mice and Metabolic Health
The research team tested the experimental drug on mice, comparing results between those receiving semaglutide alone and those receiving the combination treatment. Mice treated with only semaglutide lost 10 percent of their lean muscle mass. In contrast, mice receiving both the RNA therapy and semaglutide lost just 5.5 percent of their lean muscle mass.
Total fat loss also favored the combination therapy. Mice taking semaglutide alone retained an average of 8 grams of body fat, while mice receiving both treatments retained only 4 grams of body fat. Beyond weight measurements, the mice receiving the RNA therapy showed improvements in metabolic health and glucose tolerance.
Next Steps for Drug Development
Ionis Pharmaceuticals, a company specializing in RNA-based therapeutics, collaborated with Joseph Bass and his research team at Northwestern to develop the drug. Following the animal trials, the research team plans to test the theory on human cells. Northwestern has already filed a provisional patent application for the experimental treatment.
“We have identified, for the first time, an RNA therapy that promotes thermogenesis and, when combined with the GLP-1 drug semaglutide, helps preserve lean muscle mass,” said Joseph Bass, the study’s senior author and director of the center for diabetes and metabolism at Northwestern’s Feinberg School of Medicine.
Questions About the New RNA and Semaglutide Combination
What specific gene does the experimental RNA therapy target?
The RNA-based treatment targets and silences the ZFP423 gene, which normally slows white fat from converting into energy-burning beige fat.
How much lean muscle did mice save using both drugs?
Mice taking both the RNA therapy and semaglutide lost 5.5 percent of their lean muscle mass, whereas mice taking semaglutide alone lost 10 percent.
Which pharmaceutical company helped develop the treatment?
Ionis Pharmaceuticals, a firm specializing in RNA-based therapies, worked with researchers at Northwestern University to develop the drug.
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