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Review
. 2004 Oct 5;101 Suppl 2(Suppl 2):14599-606.
doi: 10.1073/pnas.0404874101. Epub 2004 Aug 11.

Autoimmune concepts of multiple sclerosis as a basis for selective immunotherapy: from pipe dreams to (therapeutic) pipelines

Reinhard Hohlfeld  1 , Hartmut Wekerle
Affiliations
Review

Autoimmune concepts of multiple sclerosis as a basis for selective immunotherapy: from pipe dreams to (therapeutic) pipelines

Reinhard Hohlfeld et al. Proc Natl Acad Sci U S A. .

Abstract

Autoimmune T and B cell responses to CNS antigen(s) are thought to drive the pathogenesis of multiple sclerosis (MS), and thus are logical targets for therapy. Indeed, several immunomodulatory agents, including IFN-beta 1b, IFN-beta 1a, glatiramer acetate, and mitoxantrone, have had beneficial clinical effects in different forms of MS. However, because the available treatments are only partially effective, MS therapy needs to be further improved. Selective (antigen-specific) immunotherapies are especially appealing because in theory they combine maximal efficacy with minimal side effects. Indeed, several innovative immunotherapies have been successfully applied in experimental autoimmune encephalomyelitis. For example, autoreactive T cells can be selectively targeted by means of antigen, T cell receptor, or activation markers. However, experimental autoimmune encephalomyelitis is far from being a perfect approximation of MS because MS is more heterogeneous and the target antigen(s) is (are) not known. Further advances in MS therapy will depend on our growing understanding of the pathogenesis of this still incurable disease.

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Figures

Fig. 1.
Fig. 1.
Proposed strategy for the identification of the unknown targets antigens of MS, starting with the characterization of the antigen-specific TCRs expressed by autoaggressive T cell infiltrates in biopsy tissue (16).
Fig. 2.
Fig. 2.
Proposed mechanism of action of GA, an approved agent for the immunomodulatory treatment of relapsing-remitting MS. See text for details.
See this image and copyright information in PMC

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