Mitochondrial hydrogen sulfide supplementation improves health in the C. elegans Duchenne muscular dystrophy model
Ellwood RA., Hewitt JE., Torregrossa R., Philp AM., Hardee JP., Hughes S., van de Klashorst D., Gharahdaghi N., Anupom T., Slade L., Deane CS., Cooke M., Etheridge T., Piasecki M., Antebi A., Lynch GS., Philp A., Vanapalli SA., Whiteman M., Szewczyk NJ.
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.