Urolithin A shows promise to slow the progression of Duchenne muscular dystrophy

The progression of Duchenne muscular dystrophy (DMD) can be delayed in mice by adding their diet with urolithin A, according to new results published today. Findings published in Science Translational Medicine, raises hopes that new treatment options for DMD, an incurable genetic condition characterized by progressive muscle degeneration, could one day develop. Approximately 1 in 3,500 boys is born with DMD, which usually develops in childhood and significantly reduces life expectancy.

New research conducted in the laboratory of Professor Johan Auwerx, Ph.D. Sc. At the Swiss Federal Institute of Technology EPFL and the University of Lausanne, in collaboration with scientists from the Swiss life science company Amazentis, he highlights the important role that defective mitochondria can play in DMD.

Mitochondrial cell cells produce the energy needed for normal muscle function. But muscle cells taken from both human patients with DMD and mice bred to mimic the condition show significant deficiencies in mitochondrial activity, the study found. In particular, gene expression patterns show that the development of DMD is associated with a significant reduction in mitophagy – process cells rely on the removal and recycling of defective mitochondria and the maintenance of high energy levels.

Duchenne muscular dystrophy is the most common fatal genetic disease diagnosed in childhood, but no cure is yet available. Our work represents a significant breakthrough in the search for new therapeutic approaches for muscular dystrophies. “

Johan Auwerx, Ph.D. Med., Lead Author and Professor, EPFL

The natural compound Urolitin A is known to activate mitophagy and improve mitochondrial health in both mice and humans. When the study’s scientists and lead authors, Peiling Luan and Davide D’Amico, fed the compound DMD mice for only ten weeks, they saw how mitophagy levels effectively increased by returning them to normal. This has led to a significant reduction in muscle damage and improved muscle health and performance. DMD mice administered urolithin A recorded a 31% increase in grip strength and a 45% increase in running performance compared to control untreated animals. And they lived longer – survival increased by 40%.

Important for human disease, Urolitin A reduced a harmful condition called fibrosis in the muscles of the DMD mouse heart and diaphragm by 36% and 39%, respectively. Similar damage seen in DMD patients usually leads to fatal heart or respiratory failure. Urolithin A could also enhance the regeneration of muscle stem cells. This is especially important for the disease in humans because the onset of DMD is associated with depletion of functional stem cells.

Davide D’Amico, Ph.D., project manager at Amazentis and first author, said: “Prior to this study, it was understood that dramatic loss of muscle function in DMD patients was associated with mitochondrial dysfunction. Here we found that defective mitophagia, removal and recycling dysfunctional mitochondria, plays a key role in the progression of DMD. “

Chris Rinsch, Ph.D., co-founder and CEO of Amazentis, said, “Strict science published in Science Translational Medicine strengthens the scientific evidence of urolithin A as a potent enhancer of muscle function. It is exciting to see how this natural metabolite can support not only healthy muscles, but also promises progressive muscle disease in preclinical research. “


Ecole Polytechnique Fédérale de Lausanne

Journal reference:

Luan, P., and others. (2021) Urolitin A improves muscle function by inducing mitophagia in muscular dystrophy. Science Translational Medicine. doi.org/10.1126/scitranslmed.abb0319.