Increasing evidence implicates oxidative damage as a major mechanism in the pathogenesis of amyotrophic lateral sclerosis (ALS). We examined the effect of preventative treatment with N-acetyl-L-cysteine (NAC), an agent that reduces free radical damage, in transgenic mice with a superoxide dismutase (SOD1) mutation (G93A), used as an animal model of familial ALS. NAC was administered at 1% concentration in the drinking water from 4–5 weeks of age. The treatment caused a significantly prolonged survival and delayed onset of motor impairment in G93A mice treated with NAC compared to control mice. These results provide further evidence for the involvement of free radical damage in the G93A mice, and support the possibility that NAC, an over-the-counter antioxidant, could be explored in clinical trials for ALS.
1Neurochemistry Laboratory, Neurology Service, Massachusetts General Hospital and Harvard Medical School, Boston, MA
2Neurology Department, New York Hospital-Cornell Medical Center, New York, NY, USA
3Laboratory for Oxidation Biology, Genetics and Aging Unit, Massachusetts General Hospital East and Harvard Medical School, Bldg 149, 13th Street, Charlestown, MA 02129
4Corresponding Author: Ashley I. Bush
Received 9 May 2000; accepted 25 May 2000