title: Benefit of a combined treatment with trientine and ascorbate in familial amyotrophic lateral sclerosis model mice.
abstract: We previously reported that the common toxic gain-of-function in various mutant copper-zinc superoxide dismutases (SOD1) seen in patients with familial amyotrophic lateral sclerosis (ALS) was an abnormal copper release from the enzyme protein. In this study, trientine and ascorbate, known to have a beneficial effect in an animal model of Wilson disease, were administered to 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 the treated group was delayed as well. Since the agents used in this study cause low toxicity in animals and humans, this treatment may be a good candidate for clinical application.
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology*; D003300:Copper / Q000378:metabolism; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D014266:Trientine / Q000494:pharmacology*