Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy, and despite improvements in genetic and pharmacological pathology, its management remains a significant challenge.
In a new study, scientists have sown that supplementing mice with Urolithin A can delay Duchenne Muscular Dystrophy’s progression (DMD). The discovery offers unique treatments for DMD and highlights the critical role that defective mitochondria can play in DMD.
The study was done by EPFL professor Johan Auwerx and scientists from EPFL start-up Amazentis.
The Mitochondria, the powerhouse of the cell, generates vital energy for normal muscle function. In this study, scientists found that muscle cells taken from both human DMD patients and mice bred to mimic the condition show significant defects in mitochondrial activity.
Specifically, gene expression patterns show that the advancement of DMD is related to a marked decrease in mitophagy – the process cells depend on to eliminate and reuse defective mitochondria and keep up energy levels.
Johan Auwerx, EPFL’s Laboratory of Integrative Systems Physiology of Professor said, Duchenne Muscle Dystrophy is the most common fatal genetic disease diagnosed in childhood with still no cure available. Our work represents a significant breakthrough in the search for new therapeutic approaches for muscular dystrophies.
During the study, scientists fed DMD mice with Urolithin A for just ten weeks. Tey observed mitophagy levels rise effectively, restoring them to normal.
This improvement was reflected in a drastic reduction of muscle damage and gains in muscle health and performance. The DMD mice directed Urolithin A saw grasp strength increase by 31% and running execution increment by 45% compared with untreated control animals. Furthermore, they lived longer – survived by 40%.
Significantly for the human disease, Urolithin A reduced a damaging condition called fibrosis in muscles of the DMD mouse heart and diaphragm by 36% and 39%, respectively. Similar damage is seen in DMD patients typically leads to fatal cardiac or respiratory failure.
Davide D’Amico, Ph.D., Project Leader at Amazentis and a first author of the paper, said: “Before this study, it was understood that the dramatic loss of muscle function in DMD patients was associated with mitochondrial dysfunctions. Here we discovered that mitophagy, the removal, and recycling of dysfunctional mitochondria, plays a key role in the progression of DMD when defective.”
Chris Rinsch, Ph.D., Co-founder, and CEO of Amazentis, said, “The rigorous science being published in Science Translational Medicine strengthens the scientific evidence of Urolithin A as a potent muscle function enhancer. It’s exciting to see this natural metabolite can support healthy muscle and show promise for progressive muscle diseases in pre-clinical research.
- Peiling Luan et al., Urolithin A improves muscle function by inducing mitophagy in muscular dystrophy. DOI: 10.1126/scitranslmed.abb0319