Department of Neurology, Ann Romney Center for Neurologic Diseases, Partners MS Center, Evergrande Center for Immunologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Department of Neurology, Ann Romney Center for Neurologic Diseases, Partners MS Center, Evergrande Center for Immunologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Neuron. 2018 Feb 21;97(4):742-768. doi: 10.1016/j.neuron.2018.01.021.
Multiple sclerosis (MS) is an autoimmune disease triggered by environmental factors that act on a genetically susceptible host. It features three clinical stages: a pre-clinical stage detectable only by MRI; a relapsing-remitting (RRMS) stage characterized by episodes of neurologic dysfunction followed by resolution; and a progressive stage, which usually evolves from the relapsing stage. Advances in our understanding of the immune mechanisms that contribute to MS have led to more than ten FDA-approved immunotherapeutic drugs that target effector T cells, regulatory cells, B cells, and cell trafficking into the nervous system. However, most drugs for relapsing MS are not effective in treating progressive disease. Progressive MS features a compartmentalized immune response in the central nervous system, involving microglia cells and astrocytes, as well as immune-independent processes that drive axonal dysfunction. Major challenges for MS research involve understanding the mechanisms of disease progression, developing treatment for progressive MS, and determining the degree to which progressive disease can be prevented by early treatment. Key priorities for MS research include developing biomarkers, personalized medicine and advanced imaging, and a better understanding of the microbiome. With a better understanding of the genetic and epidemiological aspects of this disease, approaches to prevent MS are now also being considered.
多发性硬化症（MS）是一种由环境因素引发的自身免疫性疾病，作用于遗传易感宿主。它有三个临床阶段：在 MRI 下才可检测到的临床前期；以神经功能障碍发作随后缓解为特征的复发缓解（RRMS）期；以及通常从复发期发展而来的进展期。我们对导致 MS 的免疫机制的理解的进步，导致了十种以上获得 FDA 批准的免疫治疗药物，这些药物针对效应 T 细胞、调节细胞、B 细胞和细胞向神经系统的迁移。然而，大多数用于治疗复发 MS 的药物在治疗进展性疾病方面效果不佳。进展性 MS 以中枢神经系统的分隔免疫反应为特征，涉及小胶质细胞和星形胶质细胞，以及驱动轴突功能障碍的免疫独立过程。MS 研究的主要挑战包括了解疾病进展的机制、为进展性 MS 开发治疗方法，以及确定早期治疗可以在多大程度上预防进展性疾病。MS 研究的重点包括开发生物标志物、个性化药物和先进的成像技术，以及更好地了解微生物组。随着对这种疾病的遗传和流行病学方面的更好理解，现在也在考虑预防 MS 的方法。
