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Int. J. Mol. Sci. 2017, 18(9), 1992; doi:10.3390/ijms18091992

Monoclonal Antibodies in Preclinical EAE Models of Multiple Sclerosis: A Systematic Review

Institute of Clinical Pharmacology, University Hospital Frankfurt, 60590 Frankfurt, Germany
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Received: 30 August 2017 / Revised: 12 September 2017 / Accepted: 13 September 2017 / Published: 16 September 2017
(This article belongs to the Special Issue Advances in Multiple Sclerosis 2017)
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Abstract

Monoclonal antibodies (mAb) are promising therapeutics in multiple sclerosis and multiple new candidates have been developed, hence increasing the need for some agreement for preclinical mAb studies. We systematically analyzed publications of experimental autoimmune encephalomyelitis (EAE) studies showing effects of monoclonal antibodies. A PubMed search retrieved 570 records, out of which 122 studies with 253 experiments were eligible based on experimental design, number of animals and presentation of time courses of EAE scores. Analysis of EAE models, treatment schedules, single and total doses, routes of administration, and onset of treatment from pre-immunization up to 35 days after immunization revealed high heterogeneity. Total doses ranged from 0.1 to 360 mg/kg for observation times of up to 35 days after immunization. About half of experiments (142/253) used total doses of 10–70 mg/kg. Employing this range, we tested anti-Itga4 as a reference mAb at varying schedules and got no, mild or substantial EAE-score reductions, depending on the mouse strain and onset of the treatment. The result agrees with the range of outcomes achieved in 10 reported anti-Itga4 experiments. Studies comparing low and high doses of various mAbs or early vs. late onset of treatment did not reveal dose-effect or timing-effect associations, with a tendency towards better outcomes with preventive treatments starting within the first week after immunization. The systematic comparison allows for extraction of some “common” design characteristics, which may be helpful to further assess the efficacy of mAbs and role of specific targets in preclinical models of multiple sclerosis. View Full-Text
Keywords: autoimmune encephalomyelitis; monoclonal antibody; immune system; multiple sclerosis autoimmune encephalomyelitis; monoclonal antibody; immune system; multiple sclerosis
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Schmitz, K.; Geisslinger, G.; Tegeder, I. Monoclonal Antibodies in Preclinical EAE Models of Multiple Sclerosis: A Systematic Review. Int. J. Mol. Sci. 2017, 18, 1992.

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