Animal models of multiple sclerosis—Potentials and limitations

Research highlights

▶ The classical MOG _35-55-EAE is complemented by novel cortical and toxic MS models. ▶ Putative autoantigens of EAE/MS include myelin and axonal glycoproteins and lipids. ▶ MS risk genes involve DRB1*1501 and more than 10 novel candidate genes. ▶ Treg and Th17 cells deserve close attention in EAE/MS pathogenesis. ▶ Oral disease-modifiers and monoclonal antibodies show great promise for MS therapy.

Abstract

Experimental autoimmune encephalomyelitis (EAE) is still the most widely accepted animal model of multiple sclerosis (MS). Different types of EAE have been developed in order to investigate pathogenetic, clinical and therapeutic aspects of the heterogenic human disease. Generally, investigations in EAE are more suitable for the analysis of immunogenetic elements (major histocompatibility complex restriction and candidate risk genes) and for the study of histopathological features (inflammation, demyelination and degeneration) of the disease than for screening of new treatments. Recent studies in new EAE models, especially in transgenic ones, have in connection with new analytical techniques such as microarray assays provided a deeper insight into the pathogenic cellular and molecular mechanisms of EAE and potentially of MS. For example, it was possible to better delineate the role of soluble pro-inflammatory (tumor necrosis factor-α, interferon-γ and interleukins 1, 12 and 23), anti-inflammatory (transforming growth factor-β and interleukins 4, 10, 27 and 35) and neurotrophic factors (ciliary neurotrophic factor and brain-derived neurotrophic factor). Also, the regulatory and effector functions of distinct immune cell subpopulations such as CD4 ⁺ Th1, Th2, Th3 and Th17 cells, CD4 ⁺FoxP3 ⁺ Treg cells, CD8 ⁺ Tc1 and Tc2, B cells and γδ ⁺ T cells have been disclosed in more detail. The new insights may help to identify novel targets for the treatment of MS. However, translation of the experimental results into the clinical practice requires prudence and great caution.