title: The efficacy of trientine or ascorbate alone compared to that of the combined treatment with these two agents in familial amyotrophic lateral sclerosis model mice.
abstract: One of the hypotheses regarding the pathogenesis of familial ALS (FALS) is a copper-mediated oxidative toxicity derived from the mutant Cu, Zn-superoxide dismutase (SOD1). We have previously demonstrated the efficacy of the combined treatment with a copper chelator (trientine) and an antioxidant (ascorbate) on the disease expression of the FALS-linked mutated SOD1 transgenic mice. Here, we investigated the efficacy of trientine or ascorbate alone on FALS mice when administered before or after the onset of the disease. The mice with a high dose of trientine or ascorbate administered before the onset survived significantly longer than the control. In the combined treatment with a high dose of trientine and ascorbate initiated before the onset, survival lengthened and the motor function of the mice remained more significantly than the control. None of the treatments affected the mean age of the onset, and none of the agents administered after the onset prolonged survival. These findings suggest that better outcomes may be expected by the administration of these agents at the preonset stage of the disease, and the combination of the agents acting on different sites might be useful in preserving the motor performance in FALS.
authors.affiliation: Department of Neurology, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Nagano
authors.forename: Yuuichi
authors.initials: Y
authors.lastname: Fujii
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Mitsue
authors.initials: M
authors.lastname: Taniyama
authors.forename: Kei
authors.initials: K
authors.lastname: Fukada
authors.forename: Takehiko
authors.initials: T
authors.lastname: Yanagihara
authors.forename: Saburo
authors.initials: S
authors.lastname: Sakoda
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000235:genetics; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use*; D002614:Chelating Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D015996:Survival Rate; D016896:Treatment Outcome; D014266:Trientine / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D002614:Chelating Agents; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D001205:Ascorbic Acid; D014266:Trientine