The challenge of multiple sclerosis: How do we cure a chronic heterogeneous disease?

Multiple sclerosis is (MS) a T‐cell autoimmune disease characterized by a relapsing‐remitting followed by a progressive phase. Relapses are driven by the adaptive immune system and involve waves of T helper cell 1 (Th1), Th17, and CD8 cells that infiltrate the nervous system and provoke a attack. Th...

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Vydané v:Annals of neurology Ročník 65; číslo 3; s. 239 - 248
Hlavný autor: Weiner, Howard L.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.03.2009
Wiley-Liss
Predmet:
Biological and medical sciences
Biomarkers
Disease Progression
Humans
Immunity, Innate
Immunotherapy - methods
Lymphocytes - immunology
Magnetic Resonance Imaging
Medical sciences
Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis
Multiple Sclerosis, Chronic Progressive - diagnosis
Multiple Sclerosis, Chronic Progressive - etiology
Multiple Sclerosis, Chronic Progressive - immunology
Multiple Sclerosis, Chronic Progressive - therapy
Nervous System - pathology
Neurology
Nervous system diseases
Multiple sclerosis
Cure
Chronic disease
Central nervous system disease
Inflammatory disease
ISSN:0364-5134, 1531-8249, 1531-8249
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Popis
Shrnutí:Multiple sclerosis is (MS) a T‐cell autoimmune disease characterized by a relapsing‐remitting followed by a progressive phase. Relapses are driven by the adaptive immune system and involve waves of T helper cell 1 (Th1), Th17, and CD8 cells that infiltrate the nervous system and provoke a attack. These cells are modulated by regulatory T and B cells. Infiltration of T cells into the nervous system initiates a complex immunological cascade consisting of epitope spreading, which triggers new attacks, and activation of the innate immune system (microglia, dendritic cells, astrocytes, B cells), which leads to chronic inflammation. The secondary progressive phase is due to neurodegeneration triggered by inflammation and is driven by the innate immune system. Why a shift to the progressive stage occurs and how to prevent it is a central question in MS. Effective treatment of MS must affect multiple disease pathways: suppression of proinflammatory T cells, induction of regulatory T cells, altering traffic of cells into the nervous system, protecting axons and myelin, and controlling innate immune responses. Without biomarkers, the clinical and pathological heterogeneity of MS makes treatment difficult. Treatment is further hampered by untoward adverse effects caused by immune suppression. Nonetheless, major progress has been made in the understanding and treatment of MS. There are three definitions of cure as it applies to MS: (1) halt progression of disease, (2) reverse neurological deficits, and (3) prevent MS. Although the pathways to each of these cures are linked, each requires a unique strategy. Ann Neurol 2009;65:239–248
Bibliografia:istex:12A16830CAB099B7396CBAAF88FDED698A54752D
Adapted from John Dystel Lecture. May 1, 2007. American Academy of Neurology, Boston, MA.
Potential conflict of interest: Nothing to report.
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ArticleID:ANA21640
ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:0364-5134
1531-8249
1531-8249
DOI:10.1002/ana.21640