Immunotherapy for Multiple Sclerosis: Basic Insights for New Clinical Strategies

Athanasia      Mouzaki; Theodore      Tselios; Panagiotis      Papathanassopoulos; Ioannis      Matsoukas; Kokona      Chatzantoni

Abstract

Multiple Sclerosis (MS) is a chronic inflammatory degenerative disease of the central nervous system (CNS), first described over 100 years ago. MS is a clinically heterogeneous disease with an increasing incidence over time, and a population prevalence that increases with distance from the equator. It is postulated that environmental factors such as diet and population-specific genetics, influence the distribution of MS. Diagnosis is based on established clinical criteria, aided by magnetic resonance imaging, evoked potential recordings and cerebrospinal fluid examination. Whichever the type of clinical manifestation, MS is considered an organ-specific autoimmune disease, characterized by T-cell and macrophage infiltrates, triggered by CNS-specific CD4 T-cells. The prominent autoimmune etiology of MS is considered to be the aberrant activation of IFN-γ-producing Th1 cells that recognize self-peptides of the myelin sheath, such as myelin basic protein (MBP) and proteolipid protein (PLP). Current treatments for MS aim primarily to suppress T-cell-mediated immune responses, albeit non-specifically. Experimental approaches towards the therapeutic management of MS involve the use of peptide analogs of disease-associated myelin epitopes or vaccines, to help shift T helper cell responses from Type-1 (secreting pro-inflammatory cytokines) to Type-2 (secreting anti-inflammatory cytokines) or induce peripheral Tcell tolerance. Animal models of MS have been useful to dissect disease mechanisms and evaluate new therapies. Experimental clinical trials, although few, are valuable to assess new treatment regimens and clarify possible conceptual mistakes about the disease. This review attempts to link the current knowledge of MS pathogenesis with clinical and experimental protocols of immunotherapy for MS.

Keywords: multiple sclerosis, cytokines, peptides, experimental protocols, immunotherapy

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