Benefit of a combined treatment with trientine and ascorbate in familial amyotrophic lateral sclerosis model mice

We previously reported that the common toxic gain-of-function in various mu tant copper-zinc superoxide dismutases (SOD1) seen in patients with familia l amyotrophic lateral sclerosis (ALS) was an abnormal copper release from t he enzyme protein. In this study, trientine and ascorbate, known to have a beneficial effect in an animal model of Wilson disease, were administered t o transgenic mice overexpressing a mutated human SOD1 (G93A). The onset of neurological signs in the treated group was significantly delayed compared with that in the control group, and the time to reach total paralysis in th e treated group was delayed as well. Since the agents used in this study ca use low toxicity in animals and humans, this treatment may be a good candid ate for clinical application. (C) 1999 Elsevier Science Ireland Ltd. All ri ghts reserved.