Increased oxidative damage to DNA in ALS patients

Although the cause of amyotrophic lateral sclerosis (ALS) is unknown, subst antial evidence indicates that oxidative toxicity is associated with neuron al death in this disease. We examined levels of a well-established marker o f oxidative damage to DNA, 8-hydroxy-2'-deoxyguanosine (8OH2'dG) in plasma, urine, and cerebrospinal fluid (CSF) at a single time point from subjects with ALS, other neurological diseases, or no known disorders. We also measu red the rate of change of 8OH2'dG levels in plasma and urine from ALS and i n urine from control subjects over 9 months and examined the relationship t o disease severity. In each fluid, 8OH2'dG levels were significantly elevat ed in the ALS group as compared to control subjects. In all subjects, the p lasma and CSF 8OH2'dG levels increased with age, providing further evidence for a role of oxidative damage in normal aging. Plasma and urine sOH2'dG l evels increased significantly with time in the ALS group only. The rate of increase in urine 8OH2'dG levels with time was significantly correlated wit h disease severity. These findings are consistent with the hypothesis that oxidative pathology accompanies the neurodegenerative process in ALS and su ggest that 8OH2'dG may provide a useful tool for monitoring therapeutic int erventions in this disease. (C) 2000 Elsevier Science Inc.