De Jager Philip L, Hafler David A
Center for Neurologic Diseases, Department of Neurology, Brigham & Women's Hospital, Boston, Massachusetts 02115, USA.
Annu Rev Med. 2007;58:417-32. doi: 10.1146/annurev.med.58.071105.111552.
Although several therapies exist for multiple sclerosis (MS), the most common inflammatory demyelinating disease of the central nervous system (CNS), there remains a large unmet clinical need for more effective immunomodulatory treatments in this category of diseases and for interventions that address their neurodegenerative component, which is currently untreated. Progress in our understanding of the immunology of MS over the past 30 years has recently synergized with novel computational methods and emerging high-throughput technologies that characterize variations in DNA, RNA, proteins, and metabolites to usher in a period of intense pathophysiologic investigation. These efforts are beginning to define subsets of patients with different forms of demyelinating disease. This partitioning of patients will prove valuable as we begin to tailor immunotherapy to the underlying pathophysiologic processes of individual patients using current therapies, emerging treatments, and rational combinations of all of these treatments. Preventing the entry of lymphocytes into the CNS and modifying the nature of the immune response are treatment approaches that work in the inflammatory component of MS but have little or no effect on neurodegeneration. Two challenges confront us: to develop cocktails of therapies that shift the immune homeostasis of patients with MS toward a healthy profile, and to identify and modulate the activity of targets within the neurodegenerative component of MS.
虽然针对多发性硬化症（MS）——中枢神经系统（CNS）最常见的炎性脱髓鞘疾病，已有多种治疗方法，但对于这类疾病中更有效的免疫调节治疗以及针对其目前未得到治疗的神经退行性成分的干预措施，临床上仍存在很大的未满足需求。在过去30年里，我们对MS免疫学的理解取得的进展，最近与新型计算方法以及新兴的高通量技术协同作用，这些技术可对DNA、RNA、蛋白质和代谢物的变异进行表征，从而开启了一个深入病理生理学研究的时期。这些努力开始界定不同形式脱髓鞘疾病患者的亚组。随着我们开始使用现有疗法、新兴疗法以及所有这些疗法的合理组合，根据个体患者的潜在病理生理过程来定制免疫疗法，这种对患者的划分将被证明是有价值的。阻止淋巴细胞进入中枢神经系统以及改变免疫反应的性质，是在MS的炎性成分中起作用但对神经退行性变几乎没有影响或没有影响的治疗方法。我们面临两个挑战：开发能将MS患者的免疫稳态转变为健康状态的联合疗法，以及识别并调节MS神经退行性成分内靶点的活性。
