A recent study published in the Journal of Cachexia, Sarcopenia and Muscle found that the immune-targeting drug ONX-0914 improves muscle strength and gut microbiome composition in a mouse model of Duchenne muscular dystrophy (DMD).
ONX-0914 is an immunoproteasome (IP) inhibitor, meaning it blocks the activity of certain proteins that activate the immune system. In patients with DMD, changes in the immune system are known to impact muscle health by triggering inflammation and impeding muscle repair.
The IP is highly active in the gut. Therefore, in their study, the authors sought to determine whether IP inhibitors may alter the gut microbiome in DMD mice, and whether those alterations affect muscle function.
Results showed that mice treated with ONX-0914 experienced increased fecal weight, which indicates improved intestinal function and motor activity.
Read more about DMD therapies
When these mice were given antibiotics, however, the impacts of ONX-0914 were diminished. “These findings demonstrate that ONX-0914’s efficacy on intestinal inflammation is dependent on the presence of a functional gut microbiota,” the researchers explained.
The treated mice also had greater muscle fiber size and strength compared to the antibiotic-treated mice, further supporting the importance of communication between the gut and muscles. Treated mice had lower levels of creatine kinase, a marker of muscle damage, as well.
What is creatine kinase?
Creatine kinase (CK) is an enzyme found in muscles. When muscles become damaged, CK leaks out of the muscles and into the bloodstream. In diagnosing DMD, CK levels are checked in a blood sample and if they are unusually high, this is a key indicator of DMD.
Further analysis revealed that ONX-0914-treated mice had enriched fatty acid and sugar metabolism pathways that are critical for maintaining intestinal function. Metabolic improvements were also seen in the skeletal muscle, showing that the effects of ONX-0914 extended beyond the gut microbiome.
“Our study advances the understanding of the role of dysbiosis in DMD disease and identifies IP inhibition as a potential therapeutic strategy to modulate the dystrophic gut–muscle axis, offering new perspectives for microbiota-targeted therapies,” the authors concluded.
Sign up here to get the latest news, perspectives, and information about DMD sent directly to your inbox. Registration is free and only takes a minute.
