Vosslamber Saskia, van Baarsen Lisa G M, Verweij Cornelis L
VU University Medical Center, Deptartment of Pathology, Amsterdam, The Netherlands.
Pharmacogenomics. 2009 Jan;10(1):97-108. doi: 10.2217/14622416.10.1.97.
Multiple sclerosis (MS) is an inflammatory disease of the CNS. The clinical presentation of MS is heterogeneous. Interferons (IFNs) were the first agents to show clinical efficacy in the treatment of MS and prolonged treatment is still the best available therapy. Although IFN treatment ameliorates immune dysfunction, the response is partial. Clinical experience indicates that there are responders and nonresponders. This distinction suggests that a subset of patients are insensitive or resistant to the action of IFN. This implies that pharmacodynamic responses may differ between patients, leading to interindividual differences in clinical response. Understanding of the factors that underlie the therapeutic response is key to the identification of predictive markers. Here, we describe novel developments in pharmacogenomics research to improve the understanding of the pharmacological effects of IFN therapy, and the identification of biomarkers that allow stratification of MS patients for their response to IFN-beta. Ultimately, this information will lead to a personalized form of medicine, whereby a specific therapy will be applied that is best suited to an individual patient.
多发性硬化症（MS）是一种中枢神经系统的炎症性疾病。MS的临床表现具有异质性。干扰素（IFN）是首批显示出治疗MS临床疗效的药物，长期治疗仍是目前最佳的可用疗法。尽管IFN治疗可改善免疫功能障碍，但反应是部分性的。临床经验表明，存在反应者和无反应者。这种差异表明，一部分患者对IFN的作用不敏感或有抗性。这意味着患者之间的药效学反应可能不同，导致临床反应存在个体差异。了解治疗反应背后的因素是识别预测标志物的关键。在此，我们描述了药物基因组学研究的新进展，以增进对IFN治疗药理作用的理解，以及识别可将MS患者根据其对IFN-β的反应进行分层的生物标志物。最终，这些信息将促成个性化医疗形式，即应用最适合个体患者的特定疗法。
