Experimental allergic encephalomyelitis: A misleading model of multiple sclerosis

Abstract

Despite many years of intensive research, multiple sclerosis (MS) defies understanding and treatment remains suboptimal. The prevailing hypothesis is that MS is immune mediated and that experimental allergic encephalomyelitis (EAE) is a suitable model to elucidate pathogenesis and devise therapy. This review examines critically the validity that EAE is an adequate and useful animal model of MS and finds credible evidence lacking. EAE represents more a model of acute central nervous system inflammation than the counterpart of MS. We propose to reconsider the utilization of EAE, especially when this model is used to define therapy. This will also force us to examine MS without the restraints imposed by EAE, as to what it is, rather than what it looks like.

Cytosolic Phospholipase A2α Blockade Abrogates Disease during the Tissue-Damage Effector Phase of Experimental Autoimmune Encephalomyelitis by Its Action on APCs

“…The existing animal models of EAE that are used during drug development have been inconsistent in their ability to predict clinical outcomes of these drugs in MS (6,32,45). A case in point is that although the anti-p40 Abs were shown to be efficacious in several EAE models (9)(10)(11)46), they met with failure in the clinical trials of MS (14-16).…”

“…B10.PL mice were immunized with MBP [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] and were treated with vehicle or WAY-196025 100 mg/kg, s.c., once per day for 8 d, and their spleens were isolated. APCs were isolated from these vehicle-treated or WAY-196025-treated B10.PL mice by positive selection magnetic beads to remove CD4 + and CD8 + T cells, using the manufacturer's protocol (Invitrogen Life Technologies).…”

“…Naive anti-MBP TCR transgenic CD4 + T cells were isolated by negative selection using magnetic sorting, according to the manufacturer's protocol (Invitrogen Life Technologies). For proliferation assay, APCs were irradiated at 2000 rads and cultured with naive anti-MBP TCR transgenic CD4 + T cells in a ratio of 5:1 in presence of various amounts of MBP [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] peptide with or without TGF-b (10 ng/ml). Forty-four to forty-eight hours after the initiation of cultures, supernatant was harvested, and the cultures were pulsed with 0.5 mCi […”

Magnetic resonance imaging of experimental autoimmune encephalomyelitis in the common marmoset

“…As a proof of relevance, three therapeutics commonly used to treat MS patients have been developed on the ground of EAE models: glatiramer acetate, mitoxantrone and natalizumab (Yednock et al, 1992). However, a large number of other potential therapies effective in mice EAE failed to have clinical efficacy in human MS (Sriram and Steiner, 2005;Steinman and Zamvil, 2006). This is likely to be due to the large evolutionary distance between rodents and humans.…”

The Multitasking Mast Cell: Positive and Negative Roles in the Progression of Autoimmunity

“…The rodent model of MS, EAE, employs immunization with a myelin peptide in the context of complete Freund's adjuvant to generate disease. Although EAE is not the same disease as MS, featuring different locations of demyelination and a different makeup of cellular infiltrate into pathological plaques (23), EAE has long been considered a useful model for the understanding of MS pathology and the identification of therapeutic targets (24 -26). In both diseases, blood-brain barrier permeability is a checkpoint in disease development that allows the massive infiltrate of inflammatory cells, including T cells, into the CNS.…”