Duchenne muscular dystrophy and side effects of treatment

Duchenne muscular dystrophy (DMD) is an inherited neuromuscular disorder characterized by progressive degeneration of skeletal muscles and heart muscle. It manifests in early childhood with problems in walking that progress to loss of independence. Despite supportive care, patients have a short life span due to respiratory failure, lung infection, or cardiac arrest. To date, there is still no cure. Oral corticosteroid therapy limits the effects of the disease and improves patients' living conditions. However, chronic use of these drugs causes a number of side effects that limit their clinical use. A new alternative in supportive therapy for this serious disease comes from the laboratories of the Department of Pharmacy at the Federico II University of Naples.

In the study published in the prestigious journal Redox Biology, coordinated by Professor Mariarosaria Bucci of the Department of Pharmacy and led by Drs. Elisabetta Panza and Valentina Vellecco, it was shown for the first time that the transsulfuration pathway is severely impaired in DMD. This metabolic pathway leads to the synthesis of important endogenous sulfur antioxidants such as taurine, glutathione, and hydrogen sulfide (H2S), a gastransmitter for which several biological actions have been described in recent years. In the study it is shown that the expression levels of genes coding for key enzymes of the transsulfuration pathway, as well as the major metabolites produced, are significantly reduced both in myoblasts isolated from children with DMD and in muscles from mdx mice, a known mouse model of DMD. Oral administration of an H2S donor in these mice improved all molecular features of DMD (inflammation, fibrosis, and autophagy), resulting in a complete restoration of muscle strength.

Although great caution is always needed when interpreting results obtained in experimental models, the hope is that this scientific discovery will pave the way for new and more effective therapies for muscle disease and offer a different outlook on life for patients with Duchenne muscular dystrophy.

The study benefited from the valuable collaboration of the Institute of Biomolecular Chemistry of the National Research Council (CNR-Icb) in Pozzuoli, Italy; the Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York, USA; and the Pathology Anatomy Unit of Antonio Cardarelli Hospital in Naples, Italy.