Sulfur amino acid supplementation displays therapeutic potential in a C. elegans model of Duchenne muscular dystrophy.

Ellwood, Rebecca A.; Slade, Luke; Lewis, Jonathan; Torregrossa, Roberta; Sudevan, Surabhi; Piasecki, Mathew; Whiteman, Matthew; Etheridge, Timothy; Szewczyk, Nathaniel J.

Abstract

Mutations in the dystrophin gene cause Duchenne muscular dystrophy (DMD), a common muscle disease that manifests with muscle weakness, wasting, and degeneration. An emerging theme in DMD pathophysiology is an intramuscular deficit in the gasotransmitter hydrogen sulfide (H2S). Here we show that the C. elegans DMD model displays reduced levels of H2S and expression of genes required for sulfur metabolism. These reductions can be offset by increasing bioavailability of sulfur containing amino acids (L-methionine, L-homocysteine, L-cysteine, L-glutathione, and L-taurine), augmenting healthspan primarily via improved calcium regulation, mitochondrial structure and delayed muscle cell death. Additionally, we show distinct differences in preservation mechanisms between sulfur amino acid vs H2S administration, despite similarities in required health-preserving pathways. Our results suggest that the H2S deficit in DMD is likely caused by altered sulfur metabolism and that modulation of this pathway may improve DMD muscle health via multiple evolutionarily conserved mechanisms.

Citation

Ellwood, R. A., Slade, L., Lewis, J., Torregrossa, R., Sudevan, S., Piasecki, M., Whiteman, M., Etheridge, T., & Szewczyk, N. J. (2022). Sulfur amino acid supplementation displays therapeutic potential in a C. elegans model of Duchenne muscular dystrophy. Communications Biology, 5(1), Article 1255. https://doi.org/10.1038/s42003-022-04212-z

• Journal Article Type: Article
• Acceptance Date: Nov 1, 2022
• Online Publication Date: Nov 16, 2022
• Publication Date: Nov 16, 2022
• Deposit Date: Jan 18, 2023
• Publicly Available Date: Jan 19, 2023
• Journal: Communications Biology
• Electronic ISSN: 2399-3642
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 5
• Issue: 1
• Article Number: 1255
• DOI: https://doi.org/10.1038/s42003-022-04212-z
• Public URL: https://nottingham-repository.worktribe.com/output/14025606
• Publisher URL: https://www.nature.com/articles/s42003-022-04212-z
• PMID: 36385509