Mitochondrial hydrogen sulfide supplementation improves health in the <i>C. elegans</i> Duchenne muscular dystrophy model
Rebecca A. Ellwood, Jennifer Hewitt, Roberta Torregrossa, Ashleigh M. Philp, Justin P. Hardee, Samantha Hughes, David van de Klashorst, Nima Gharahdaghi, Taslim Anupom, Luke Slade, Colleen S. Deane, Michael P. Cooke, Timothy Etheridge, Mathew Piasecki, Adam Antebi, Gordon S. Lynch, Andrew Philp, Siva A. Vanapalli, Matthew Whiteman, Nathaniel J. Szewczyk
Abstract
Significance Duchenne muscular dystrophy (DMD) is a fatal degenerative disease without a cure. Current standard pharmacological treatment is corticosteroids. Their prolonged use is associated with several undesirable side effects. Using Caenorhabditis elegans , we have identified pharmacological treatments that supplement hydrogen sulfide (H 2 S). One, sodium GYY4137, largely acts like prednisone to improve neuromuscular health; the other, AP39, targets H 2 S delivery to mitochondria. As these are not steroids, they are unlikely to produce steroid-induced side effects. Additionally, as DMD mice show a decline in total sulfide, our results pave the way for evaluation of cellular and/or mitochondrial H 2 S in DMD pathology and warrant further investigation of selective H 2 S delivery approaches in mdx mice and/or higher animal models of DMD.