Pre-clinical evaluation of cysteamine bitartrate as a therapeutic agent for mitochondrial respiratory chain disease (worm)

Pre-clinical studies of cysteamine bitartrate demonstrate its narrow therapeutic window, where toxicity at millimolar levels correlates with a marked induction of hydrogen peroxide production. At micromolar range concentrations, cysteamine bitartrate yielded a survival benefit in RC disease subject fibroblasts, and protection from brain death in RC complex IV deficient zebrafish. Mitochondrial oxidative stress and membrane potential were significantly improved by micromolar cysteamine bitartrate in RC complex I disease worms, translating to a modest improvement of animal development and fecundity but not lifespan. Overall, these data suggest that cysteamine bitartrate may hold therapeutic potential but requires careful consideration of safe and effective dose to further evaluate in clinical trials of human subjects with primary mitochondrial disease. One wild type group, one untreated Gas-1 mutant group, one Gas-1 + Nacetylcysteine group, and 4 Gas-1 + Cysteamine groups using different dosages