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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Promotion of Remyelination by Immunoglobulins: Implications for the Treatment of Multiple Sclerosis

Author(s): C. Trebst and M. Stangel

Volume 12 , Issue 2 , 2006

Page: [241 - 249] Pages: 9

DOI: 10.2174/138161206775193118

Price: $65

Abstract

During the last decade immunomodulatory treatments have been shown to influence the natural course of multiple sclerosis (MS). However, demyelination in the central nervous system (CNS) still occurs and repair mechanisms are incomplete leading to neurological deficits. Currently, there is no therapy available to promote remyelination and thus enhance repair mechanisms. Both immunoglobulins directed against spinal cord homogenate and polyclonal immunoglobulins for intravenous use (IVIg) have been shown to support remyelination in the animal model of Theilers virus encephalomyelitis (TMEV). Further studies have identified monoclonal antibodies that lead to remyelination in TMEV and a toxic demyelination model using lysolecithin. The shared characteristics of these monoclonal antibodies are an IgM isotype and the capacity to bind oligodendrocytes, independent of epitope specificity. Recently, two human monoclonal antibodies with remyelinating properties were described. Clinical trials with IVIg have so far failed to demonstrate clinical improvement in MS patients, but these studies only employed IgG preparations. However, recent experimental data both in vivo and in vitro underline the importance of IgM for remyelination. Thus future clinical trials are needed to evaluate the remyelination potential of IgM in human diseases. The design of monoclonal antibodies capable of promoting remyelination is a telling example for the design of new specific therapies derived from biological products like polyclonal immunoglobulins.

Keywords: Multiple sclerosis, remyelination, immunoglobulin, IVIg, immunomodulation


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