Response to drug treatment in newly diagnosed epilepsy: A pilot study of 1H NMR- and MS-based metabonomic analysis
Response to drug treatment in newly diagnosed epilepsy: A pilot study of 1H NMR- and MS-based metabonomic analysis
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DOI：
10.1016/j.eplepsyres.2009.11.005
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发表时间：
2010-02-01
影响因子：
2.2
通讯作者：
Parkinson, John A.
中科院分区：
文献类型：
--
作者：
Al Zweiri, Muhammed;Sills, Graeme J.;Parkinson, John A.
了解耐药性的生物学基础并开发有助于预测结果的技术有可能彻底改变癫痫的药物治疗。我们已经进行了一项试点研究的代谢组学分析，使用核磁共振（NMR）光谱和质谱（MS），努力确定抗癫痫药物治疗的反应的代谢生物标志物。治疗前血清样本来自125名新诊断癫痫患者，他们参加了一项随机单药治疗试验。在开始治疗后6周、6个月和12个月评估结局（应答者、非应答者）。通过NMR和MS对血清样品进行研究，并通过主成分分析（PCA）询问所得数据。在研究的三个临床终点中，AED治疗应答者和非应答者的代谢特征（通过NMR或MS获得）无明显区别，表明治疗前血清样本不含任何显著的生物标志物;新发癫痫患者对初始治疗的反应性。代谢组学分析无疑适用于寻找癫痫药物治疗反应的生物学预测因子，但未来的研究应采用更大的患者队列，更具歧视性的分析，以及不那么模棱两可的临床表型。(C)2009 Elsevier B. V.保留所有权利。
Understanding the biological basis of drug resistance and developing techniques which facilitate prediction of outcome have the potential to revolutionise the pharmacotherapy of epilepsy. We have performed a pilot study of metabonomic analysis using nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) in an effort to identify metabolic biomarkers of response to antiepileptic drug treatment. Pre-treatment serum samples were obtained from 125 patients with newly diagnosed epilepsy who were taking part in a randomised monotherapy trial. Outcome (responder, non-responder) was assessed at 6 weeks, 6 months, and 12 months after starting treatment. Serum samples were subject to investigation by both NMR and MS and the resulting data interrogated by principal components analysis (PCA). There was no clear distinction in the metabolic profile, acquired by either NMR or MS, of responders and non-responders to AED treatment at any of the three clinical end-points investigated, suggesting that pre-treatment serum samples do not contain any prominent biomarkers; of responsiveness to initial treatment in new-onset epilepsy. Metabonomic analysis is undoubtedly applicable to the search for biological predictors of response to drug treatment in epilepsy, but future studies should employ larger patient cohorts, more discriminatory analyses, and a less equivocal clinical phenotype. (C) 2009 Elsevier B.V. All rights reserved.