Animal Models of Multiple Sclerosis: Imperfect but Imperative

Multiple sclerosis (MS) is a complex multifaceted disease involving autoimmune inflammation, demyelination and degeneration processes. The disease is heterogeneous in its clinical manifestation and progression, as well as in its pathological mechanisms. Animal models have been indispensable for MS research. There is however, an ongoing controversy in regard to their true relevance to the human disease.

Multiple Sclerosis

The most intensively studied MS model, experimental autoimmune encephalomyelitis (EAE), discovered as a rare complication of rabies vaccinations, has been in use for over 80 years. Immunizing rodents or nonhuman primates by self-myelin antigens/epitopes induces an autoimmune response in the CNS, which is typically manifested by ascending tail to limb paralysis. EAE is actually a group of models with different disease courses, depending on the genetic background and the antigen used for immunization. Importantly, different pathological patterns are involved in different EAE models, recapitulating the various repertoires of MS. For example, the relapsing-remitting model induced by the myelin proteolipid protein (PLP) peptide in SJL/J mice is characterized by widespread myelin damage, whereas in the chronic model induced by the myelin oligodendrocyte glycoprotein (MOG) peptide in C57BL/6 mice, axonal and neuronal damage are more prevalent. In all these animal models, as well as in MS, the pathological processes occur under an inflammatory background.

The parallels that can be drawn between the EAE models and the MS subtypes facilitated these models’ usage for investigating MS pathophysiology and therapy. However, as time went on, the limitations of the “classical” EAE models became evident. It has been demonstrated that the unique pattern of demyelination characteristic of MS is not accurately portrayed in the EAE models.

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