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The value of animal models for drug development in multiple sclerosis.
Manuel A Friese1, Xavier Montalban, Nick Willcox
1MRC Human Immunology Unit and Department of Clinical Neurology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, United Kingdom.
Brain : a Journal of Neurology
|April 26, 2006
Summary
Experimental allergic encephalomyelitis (EAE) models multiple sclerosis but treatments successful in EAE often fail in patients. Humanized mouse models may better predict treatment efficacy for multiple sclerosis.
Area of Science:
- Neuroimmunology
- Autoimmune diseases
Background:
- Experimental allergic encephalomyelitis (EAE) is a rodent model used to study multiple sclerosis (MS) pathogenesis and test therapies.
- Therapeutic strategies developed using EAE models have shown limited success or unexpected adverse effects in human MS patients.
Purpose of the Study:
- To review discrepancies between EAE pre-clinical trials and human MS patient outcomes.
- To explore reasons for the limited translatability of EAE findings to MS drug development.
- To propose improvements for pre-clinical MS research.
Main Methods:
- Review of existing literature on EAE and MS treatment trials.
- Analysis of potential genetic and environmental differences impacting disease models.
- Discussion of pathogenic concepts and model limitations.
Main Results:
- Several treatments effective in EAE pre-clinical trials have failed or caused adverse events in MS patients.
- Discrepancies are attributed to incomplete understanding of EAE pathogenesis and rodent-human differences.
- Current understanding of EAE pathogenesis is insufficient for reliable MS drug development.
Conclusions:
- Significant differences exist between EAE and human MS, limiting the predictive value of EAE for MS therapies.
- Further research is needed to understand these discrepancies and refine pre-clinical models.
- Humanized mouse models are proposed as a more systematic approach to bridge the gap between EAE and human MS for improved drug development.