Effects of an inhibitor of poly(ADP-ribose) polymerase, desmethylselegiline, trientine, and lipoic acid in transgenic ALS mice

The development of transgenic mouse models of amyotrophic lateral sclerosis (ALS) allows the testing of neuroprotective agents. We evaluated the effec ts of five agents in transgenic mice with the G93A Cu,Zn superoxide dismuta se mutation. A novel inhibitor of poly(ADP-ribose) polymerase showed no eff ects on survival. Desmethylselegiline and CGP3466 are agents that exert ant iapoptotic effects in vitro by preventing nuclear translocation of glyceral dehyde-3-phosphate dehydrogenase, They had no significant effects on surviv al in the G93A mice. Trientine, a copper chelator, produced a modest signif icant increase in survival, Similarly administration of lipoic acid in the diet produced a significant improvement in survival. These results therefor e provide evidence for potential therapeutic effects of copper chelators an d lipoic acid in the treatment of ALS. (C) 2001 Academic Press.