Success and failure in translation of findings from experimental autoimmune encephalomyelitis to multiple sclerosis
Abstract
Despite the differences between multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE), most of the knowledge on immune-mediated tissue damage in MS is based on data from EAE. Immune response– modifying therapies such as TNFα inhibitors, glatiramer acetate (GA) or natalizumab have been studied in rodents and have been translated into treatment for patients with varying success. In humans treatment with an anti TNF monoclonal antibody or a recombinant TNF receptor Ig fusion protein resulted in enhanced inflammation. In contrast, findings from GA or natalizumab have been successful in human translation. Findings of EAE studies should be interpreted carefully and should be confirmed using substances (proof of principle). Only if successful, these substances should be studied in humans.
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References
Gold R, Linington C, Lassmann H. Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research. Brain 2006; 129: 1953-1971.
Johnson KP, Brooks BR, Cohen JA et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology 1995; 45: 1268-1276.
Lassmann H, Bruck W, Lucchinetti CF. The immunopathology of multiple sclerosis: an overview. Brain Pathol 2007; 17: 210-218.
Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 2000; 47: 707-717.
Polman CH, O'Connor PW, Havrdova E et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006; 354: 899-910.
Polman CH, Reingold SC, Banwell B et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69: 292-302.
Selmaj K, Raine CS, Cross AH. Anti-tumor necrosis factor therapy abrogates autoimmune demyelination. Ann Neurol 1991; 30: 694-700.
Teitelbaum D, Meshorer A, Hirshfeld T, Arnon R, Sela M. Suppression of experimental allergic encephaloyelitis by a synthetic polypeptide. Eur J Immunol 1971; 1: 242-248.
van Oosten BW, Barkhof F, Truyen L et al. Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2. Neurology 1996; 47: 1531-1534.
Yednock TA, Cannon C, Fritz LC, Sanchez-Madrid F, Steinman L, Karin N. Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin. Nature 1992; 356: 63-66.
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