An experimental mouse model of Multiple Sclerosis (MS)
EAE shares many clinical and pathological similarities with MS. The two conditions have a related disease course that consists of neurodegeneration resulting in progressive disability. EAE is a chronic inflammatory condition characterized by the demyelination of the CNS, involving autoimmune CD4+ Th1 cells. To induce EAE, mice are immunized with an emulsion that contains a specific myelin protein fragment (antigen) needed to trigger the expansion and differentiation of myelin protein-reactive autoimmune T-cells that target and attack the myelin proteins on neurons in the CNS. Dendritic cells in tissues pick up this antigen and take it to the lymphatic system where T-cells are primed. These T-cells eventually travel to the CNS where they mediate an attack that de-myelinates axons, slowing and disrupting the transmission of neural signals. The MOG 35-55 chronic EAE model below is useful in screening novel therapeutics for efficacy in the treatment of MS.
Chronic Model: MOG 35-55
MOG is a glycoprotein important in the myelination process of the axon. When 10-week old female C57BL/6 mice are immunized with myelin oligodendrocyte protein fragment 35-55 (MOG 35-55) they develop chronic paralysis within 8-14 days that is not characterized by a remission period.
Preclinical Drug Efficacy Studies
Mice (C57BL/6, Female, 10-weeks old)
Mice are immunized with injections of the MOG/CFA emulsion followed two-hours later by the administration of pertussis toxin. On Day 2, mice receive another injection of pertussis toxin. Mice are weighed and scored daily starting on Day 7 and continuing until the completion of the study (between 21-40 days). Length of study is determined by clinical response and is at the discretion of the investigator and/or sponsor. The administration of compounds is performed as set-forth in the study protocol.
Clinical scoring of EAE disease severity, body weights, spinal column histopathology, immunohistochemistry, and cytokine profiling using ELISA and Luminex mulitplex assays
BL McRae, CL Vanderlugt, MC Dal Canto, and SD Miller. (1995) Functional evidence for epitope spreading in the relapsing pathology of experimental autoimmune encephalomyelitis. J. Exp. Med; 182: 75 – 85.
Roberto Furlan, Alessandra Bergami, Daniela Cantarella, Elena Brambilla, Masaro Taniguchi,Paolo Dellabona, Giulia Casorati, Gianvito Martino. (2003) Activation of invariant NKT cells by GalCer administration protects mice from MOG35-55-induced EAE: critical roles for administration route and IFN- Î³ Eur. J. Immunology; 33: 1830â€“1838.
Itzhack Mendel, Nicole Kerlero de Rosbo, Avraham Ben-Nun. (1995) a myelin oligodendrocyte glycoprotein peptide induces typical chronic experimental autoimmune encephalomyelitis in H-2b mice: Fine specificity and T cell receptor V expression of encephalitogenic T cells. Eur. J. Immunology; 25: 1951-59.