Improvement of preclinical animal models for autoimmune-mediated disorders via reverse translation of failed therapies

Bert A 't Hart; S Anwar Jagessar; Yolanda S Kap; Krista G Haanstra; Ingrid H C H M Philippens; Che Serguera; Jan Langermans; Michel Vierboom

doi:10.1016/j.drudis.2014.03.023

Improvement of preclinical animal models for autoimmune-mediated disorders via reverse translation of failed therapies

Drug Discov Today. 2014 Sep;19(9):1394-401. doi: 10.1016/j.drudis.2014.03.023. Epub 2014 Apr 2.

Authors

Bert A 't Hart¹, S Anwar Jagessar², Yolanda S Kap³, Krista G Haanstra⁴, Ingrid H C H M Philippens⁴, Che Serguera⁵, Jan Langermans⁶, Michel Vierboom⁴

Affiliations

¹ Biomedical Primate Research Centre, Department of Immunobiology, Rijswijk, The Netherlands; University of Groningen, Department of Neuroscience, University Medical Center, Groningen, The Netherlands; MS Center ErasMS, Rotterdam, The Netherlands. Electronic address: hart@bprc.nl.
² Biomedical Primate Research Centre, Department of Immunobiology, Rijswijk, The Netherlands; MS Center ErasMS, Rotterdam, The Netherlands.
³ Biomedical Primate Research Centre, Department of Immunobiology, Rijswijk, The Netherlands; MS Center ErasMS, Rotterdam, The Netherlands; Erasmus Medical Center Rotterdam, Department of Immunology, Rotterdam, The Netherlands.
⁴ Biomedical Primate Research Centre, Department of Immunobiology, Rijswijk, The Netherlands.
⁵ MIRCen, CEA, Fontenay-aux-Roses, France.
⁶ Department of Animal Science, Biomedical Primate Research Centre, 2288 GJ Rijswijk, The Netherlands.

PMID: 24704460
DOI: 10.1016/j.drudis.2014.03.023

Abstract

The poor translational validity of autoimmune-mediated inflammatory disease (AIMID) models in inbred and specific pathogen-free (SPF) rodents underlies the high attrition of new treatments for the corresponding human disease. Experimental autoimmune encephalomyelitis (EAE) is a frequently used preclinical AIMID model. We discuss here how crucial information needed for the innovation of current preclinical models can be obtained from postclinical analysis of the nonhuman primate EAE model, highlighting the mechanistic reasons why some therapies fail and others succeed. These new insights can also help identify new targets for treatment.

Publication types

Review

MeSH terms

Animals
Autoimmune Diseases / physiopathology*
Disease Models, Animal*
Drug Design
Encephalomyelitis, Autoimmune, Experimental / physiopathology*
Humans
Primates
Rodentia
Species Specificity
Translational Research, Biomedical / methods