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Multiple Sclerosis: Mechanisms and Immunotherapy.
Neuron ( IF 14.7 ) Pub Date : 2018-Feb-21 , DOI: 10.1016/j.neuron.2018.01.021
Clare Baecher-Allan , Belinda J. Kaskow , Howard L. Weiner

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.

中文翻译:

多发性硬化症:机制和免疫疗法。

多发性硬化症(MS)是由作用于遗传易感宿主的环境因素引发的自身免疫性疾病。它具有三个临床阶段:仅可通过MRI检测到的临床前阶段;复发-缓解(RRMS)阶段,其特征是神经功能障碍发作,然后消退;渐进阶段,通常是从复发阶段发展而来。我们对促成MS的免疫机制的理解的进步,导致了十多种FDA批准的针对效应T细胞,调节细胞,B细胞和细胞向神经系统运输的免疫治疗药物。然而,大多数用于复发性MS的药物在治疗进行性疾病中无效。进行性多发性硬化症在中枢神经系统中具有间隔性免疫反应,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非免疫依赖性过程。MS研究的主要挑战包括了解疾病进展的机制,发展进行性MS的治疗方法以及确定早期治疗可预防进展性疾病的程度。MS研究的关键优先事项包括开发生物标志物,个性化医学和先进的成像技术,以及对微生物组的更好理解。在对这种疾病的遗传和流行病学方面有了更好的了解之后,现在也正在考虑预防MS的方法。确定早期治疗可以预防进行性疾病的程度。MS研究的关键优先事项包括开发生物标志物,个性化医学和先进的成像技术,以及对微生物组的更好理解。在对这种疾病的遗传和流行病学方面有了更好的了解之后,现在也正在考虑预防MS的方法。确定早期治疗可以预防进行性疾病的程度。MS研究的关键优先事项包括开发生物标志物,个性化医学和先进的成像技术,以及对微生物组的更好理解。在对这种疾病的遗传和流行病学方面有了更好的了解之后,现在也正在考虑预防MS的方法。
更新日期:2018-02-22
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