PT期刊文章AU -康斯坦丁萨瓦盟阿里Gafson盟——查理·麦肯尼盟——保罗·马修斯TI - Tecfidera多发性硬化症患者短期调节代谢组签名(P5.346) DP - 2017年4月18日TA -神经病学PG - P5.346 VI - 88 IP - 16补充4099 - //www.ez-admanager.com/content/88/16_Supplement/P5.346.short 4100 - http://n.neurology首页.org/content/88/16_Supplement/P5.346.full所以Neurology2017 4月18日;88 AB -目的:测试是否Tecfidera(富马酸二甲酯)改变代谢组复发缓和病人(RR-MS)女士的签名。背景:Tecfidera许可疾病修饰治疗用于RR-MS的管理。其作用机理尚未完全清楚,但治疗的好处被认为是通过其抗氧化和抗炎作用介导的。在这里,我们有与Tecfidera治疗后血浆代谢变化特征,进一步阐明这些。设计/方法:等离子体27 RR-MS病人样本(12米,15 f,平均年龄为41.7±12.5,平均1.5 eds(范围1.0 - -7.0))化验了超高效液相色谱质谱(UPLC-MS)之前,Tecfidera开始后6周。主成分分析和稀疏的偏最小二乘回归是用来描述代谢物资料预处理和后治疗。具体判别后处理代谢物变化通过成对学生的学习任务,并证实了独立随机森林和支持向量机分类的test-and-train程序后潜在的样本的分公司(75%的训练,25%的测试)。判别分子被确定使用出版数据库(该公司,达勒姆,北卡罗莱纳)。结果:PCA模型识别和治疗后的样品用积极累积R2值0.35和0.51的前两个原则组件。186质荷(m / z)峰值明显不同(学生的t检验,p & lt; 0.01, corrected) 6-weeks post-treatment. As expected, many of these were associated with metabolites derived from the TCA cycle, with succinate, fumarate and malate showing a >1.5 fold change (p < 0.01). The largest difference (39.2 fold-change) post-treatment (p < 0.0001) was assigned to succinylcarnitine. This peak was independently validated using SVM and Random Forest in a ‘test-and-train’ routine as predictive of treatment ‘state’ (p < 0.005).Conclusions: UPLC-MS analysis identified a number of metabolites altered post-treatment with Tecfidera. Succinylcarnitine protects against oxidative damage in animal models of neurodegenerative disease. It may contribute to anti-oxidant mechanisms of action of Tecfidera.Disclosure: Dr. Savva has nothing to disclose. Dr. Gafson has nothing to disclose. Dr. Mckechnie has nothing to disclose. Dr. Matthews has received personal compensation for activities with Biogen, Novartis, Ixico, transparency Life Sciences, and Adelphi Communications. Dr. Matthews has received research support from GlaxoSmithKline and Biogen.