Laboratory of Molecular Cell Biology, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada; Neuroscience Research Cluster, Health Sciences Building, University of Saskatchewan, Saskatoon, SK S7K 5E5, Canada.
Department of Anatomy and Cell Biology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada; Neuroscience Research Cluster, Health Sciences Building, University of Saskatchewan, Saskatoon, SK S7K 5E5, Canada; Cameco Multiple Sclerosis Neuroscience Research Center, City Hospital, Saskatoon, SK S7K 0M7, Canada.
Cytokine Growth Factor Rev. 2015 Apr;26(2):249-61. doi: 10.1016/j.cytogfr.2014.10.008. Epub 2014 Oct 31.
Multiple sclerosis (MS) is a progressive disorder of the central nervous system, often resulting in significant disability in early adulthood. The field of pharmacogenomics holds promise in distinguishing responders from non-responders to drug treatment. Most studies on genetic polymorphisms in MS have addressed treatment with interferon-β, yet few findings have been replicated. This review outlines the barriers that currently hinder the validity, reproducibility, and inter-study comparison of pharmacogenomics research as it relates to the use of interferon-β. Notably, statistical power, varying definitions of responder status, varying assay and genotyping methodologies, and anti-interferon-β neutralizing antibodies significantly confound existing data. Future work should focus on addressing these factors in order to optimize interferon-β treatment outcomes in MS.
多发性硬化症(MS)是一种中枢神经系统的进行性疾病,常导致成年早期出现显著残疾。药物基因组学领域有望区分药物治疗的应答者和非应答者。大多数关于 MS 中遗传多态性的研究都涉及干扰素-β的治疗,但很少有发现得到重复。这篇综述概述了当前阻碍药物基因组学研究有效性、可重复性和研究间比较的障碍,这些研究与干扰素-β的使用有关。值得注意的是,统计效力、应答者状态的不同定义、不同的检测和基因分型方法以及抗干扰素-β中和抗体显著混淆了现有数据。未来的工作应集中解决这些因素,以优化 MS 中干扰素-β的治疗效果。