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Neuron. 2018 Feb 21;97(4):742-768. doi: 10.1016/j.neuron.2018.01.021.

Multiple Sclerosis: Mechanisms and Immunotherapy.

Author information

1
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.
2
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. Electronic address: hweiner@rics.bwh.harvard.edu.

Abstract

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.

PMID:
29470968
DOI:
10.1016/j.neuron.2018.01.021
[Indexed for MEDLINE]
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