Cholesterol Metabolism: A Potential Therapeutic Target in Duchenne Muscular Dystrophy

David Israeli, his student Ai Vu Hong PhD, and Fatima Amor, all members of the Progressive Dystrophies laboratory directed by Isabelle Richard at Genethon, have published the results of research offering new perspectives on the treatment of Duchenne muscular dystrophy in the Journal of Cachexia, Sarcopenia and Muscle.

The researchers characterized a mechanism of metabolic disturbances in DMD by studying 54 patients treated or not by glucocorticoid, and comparing them to a healthy control group. They used an original bioinformatic approach for the biological interpretation of the dysregulation of small RNA molecules that modify gene expression. They used the mdx mouse, a DMD animal model, to test this hypothesis in vivo.

Bioinformatic analysis suggests that when the metabolism of lipids (cholesterol and fatty acids) is disturbed, this may play a role in the pathology. Metabolic disruption causes cholesterol to build up in damaged muscles.

This research confirms that the mevalonate and cholesterol metabolic pathways are therapeutic targets of interest for Duchenne muscular dystrophy.

“In addition to stabilizing muscle fibers, the protein dystrophin also involved in intracellular signaling. A better understanding of the metabolic changes experienced by unhealthy muscle tissue will enable us to study treatments for Duchenne muscular dystrophy that would be complementary to the restoration of dystrophin expression by gene therapy Isabelle Richard’s group is currently conducting a complementary study in this area”, says David Israeli.

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