N-Acetylcysteine and cysteamine bitartrate prevent azide-induced neuromuscular decompensation by restoring glutathione balance in two novel surf1 −/− zebrafish deletion models of Leigh syndrome (LS)

https://academic.oup.com/hmg/advance-article/doi/10.1093/hmg/ddad031/7043193

This article highlights the findings of a study conducted using zebrafish, to evaluate the role of N-Acetylcysteine and cysteamine bitartrate in preventing neuromuscular depletion in patients suffering from Leigh syndrome (LS). Leigh syndrome is a mitochondrial disorder caused by genetic mutation on the SURF1 gene resulting in the depletion of the corresponding enzyme. The condition is characterized by a progressive system dysfunction involving multiple organs, neurodevelopmental depletion, and metabolic strokes. In this study, two zebrafish models carrying the surf1-/- mutation were examined in each life stage to detect the onset of symptoms, alongside examining the efficacy of N-Acetylcysteine and cysteamine bitartrate as possible treatments. Findings revealed signs of the disease during adulthood, including decreased swimming activity and presence of biochemical markers unique to the condition, such as reduced SURF1 enzyme activity, neuro and muscular degeneration. Without treatment, the zebrafish carrying the mutant gene were found to have absent heartbeat and declared brain dead. As there is no treatment for LS the efficacy of N-Acetylcysteine and cysteamine bitartrate was tested on the mutant zebrafish. Surprisingly, both substances greatly improved the symptoms of the disease once administered at a young age. Overall, this study revealed positive data for treating LS in model organisms allowing scientists to exploit this knowledge to develop a treatment for the condition once manifested in humans.