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Review
. 2012 Oct 4;13(10):12665-709.
doi: 10.3390/ijms131012665.

What do effective treatments for multiple sclerosis tell us about the molecular mechanisms involved in pathogenesis?

Katherine A Buzzard  1 , Simon A Broadley, Helmut Butzkueven
Affiliations
Review

What do effective treatments for multiple sclerosis tell us about the molecular mechanisms involved in pathogenesis?

Katherine A Buzzard et al. Int J Mol Sci. .

Abstract

Multiple sclerosis is a potentially debilitating disease of the central nervous system. A concerted program of research by many centers around the world has consistently demonstrated the importance of the immune system in its pathogenesis. This knowledge has led to the formal testing of a number of therapeutic agents in both animal models and humans. These clinical trials have shed yet further light on the pathogenesis of MS through their sometimes unexpected effects and by their differential effects in terms of impact on relapses, progression of the disease, paraclinical parameters (MRI) and the adverse events that are experienced. Here we review the currently approved medications for the commonest form of multiple sclerosis (relapsing-remitting) and the emerging therapies for which preliminary results from phase II/III clinical trials are available. A detailed analysis of the molecular mechanisms responsible for the efficacy of these medications in multiple sclerosis indicates that blockade or modulation of both T- and B-cell activation and migration pathways in the periphery or CNS can lead to amelioration of the disease. It is hoped that further therapeutic trials will better delineate the pathogenesis of MS, ultimately leading to even better treatments with fewer adverse effects.

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Figures

Figure 1
Figure 1
Schematic representation of the expanded disability status scale (EDSS).
Figure 2
Figure 2
Axial magnetic resonance imaging showing (a) hyperintense lesions (arrows) on T2 weighted images and (b) ring, gadolinium (GAD)-enhancing lesions (arrows) on T1 weighted images.
Figure 3
Figure 3
Schematic representation of multiple sclerosis (MS) pathophysiology indicating points of treatment intervention. APC antigen presenting cell; BBB blood brain barrier; C5b-9 complement complex 5b-9; CNS central nervous system; DHODH dihydroorotate dehydrogenase; FasL Fas ligand; GA glatiramer acetate; IFN interferon; IL2R interleukin 2 receptor; MHC I major histocompatibility complex I; NO nitrous oxide; Nrf2 nuclear factor (erythrocyte derived) related factor 2; S-1-P1 sphingosine-1-phosphate 1; TCR T cell receptor; VCAM-1 vascular cell adhesion molecule 1; VLA-4 very late antigen 4.
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