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
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
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DOI：
10.1016/s0014-4886(02)00014-6
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发表时间：
2003-02-01
影响因子：
5.3
通讯作者：
Sakoda, S
中科院分区：
文献类型：
--
作者：
Nagano, S;Fujii, Y;Sakoda, S
关于家族性ALS（FALS）发病机制的假说之一是铜介导的氧化毒性，其来源于突变的Cu，Zn-超氧化物歧化酶（SOD 1）。我们先前已经证明了用铜螯合剂（曲恩汀）和抗氧化剂（抗坏血酸盐）联合治疗对ALS连锁突变的SOD 1转基因小鼠的疾病表达的功效。在此，我们研究了在疾病发作之前或之后单独给予曲恩汀或抗坏血酸盐对FALS小鼠的疗效。在发病前给予高剂量曲恩汀或抗坏血酸盐的小鼠存活时间显著长于对照组。在发病前开始的高剂量曲恩汀和抗坏血酸盐的联合治疗中，小鼠的存活时间延长，运动功能保持比对照组更显著。没有一种治疗方法影响平均发病年龄，也没有一种在发病后给药的药物延长生存期。这些研究结果表明，更好的结果可能是预期这些药物的管理在发病前阶段的疾病，并在不同的网站上作用的代理的组合可能是有用的，在保留的运动性能在FALS。(C)2003 Elsevier Science（美国）。All rights reserved.
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. (C) 2003 Elsevier Science (USA). All rights reserved.