The Experimental Autoimmune Encephalomyelitis (EAE) Model:  A Gateway to Successful Translation of Multiple Sclerosis Therapies

Mansur Aliyu; Ali Akbar  Saboor-Yaraghi; Mohamad Ali Sahraian; Farshid Noorbakhsh

doi:10.18502/ijaai.v24i5.19740

Mansur Aliyu Department of Immunology, School of Public Health, Tehran University of Medical Sciences, International Campus, TUMS-IC, Tehran, Iran
Ali Akbar Saboor-Yaraghi Department of Immunology, School of Public Health, Tehran University of Medical Sciences, International Campus, TUMS-IC, Tehran, Iran
Mohamad Ali Sahraian Multiple Sclerosis Research Centre, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
Farshid Noorbakhsh Department of Immunology, Tehran University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ijaai.v24i5.19740

Keywords: Demyelination; Experimental autoimmune encephalomyelitis; Immunopathogenesis; Inflammation; Multiple sclerosis; Precision medicine; Translational research

Abstract

Multiple sclerosis (MS) is a neuroinflammatory disorder that is characterized by demyelination, neurodegeneration, and immune dysregulation. The experimental autoimmune encephalomyelitis (EAE) model has helped to elucidate MS pathophysiology and test therapies. This review synthesizes current literature on the development, applications, and translational significance of EAE models in MS research. It discusses various EAE induction protocols, including active and passive immunization, and highlights advancements such as humanized mice and induced pluripotent stem cell (iPSC)-derived neuronal models. The review evaluates the role of EAE in identifying immune pathways, validating therapeutic agents like glatiramer acetate and natalizumab, and exploring precision medicine approaches through biomarker discovery. The EAE model replicated the key features of MS, including inflammation, demyelination, and axonal loss, facilitating therapy development. However, its predictive validity faces limitations, such as heterogeneity in disease induction, underrepresentation of chronic progression, and species differences. Innovations, such as humanized mouse models and iPSC-derived neurons, show promise in addressing these challenges. EAE research has advanced biomarker-based personalized treatments, although further validation is required. Despite its widespread use, EAE has limitations in terms of variability in disease induction, incomplete MS feature replication, species-specific responses, and clinical translation. Addressing these limitations remains crucial for therapeutic development, focusing on analyzing model limitations and strategies to overcome translational barriers. This review offers immunologists a comprehensive overview of EAE's contributions of EAE to MS research and its potential to inform the development of novel therapeutic approaches for this debilitating disease.