Autoimmune encephalomyelitis in NOD mice is not initially a progressive multiple sclerosis model

• Main Authors: David Baker, Erik Nutma, Helen O'Shea, Anne Cooke, Jacqueline M. Orian, Sandra Amor
• Format: Article
• Language: English
• Published: Wiley 2019-08-01
• Series: Annals of Clinical and Translational Neurology
• Online Access: https://doi.org/10.1002/acn3.792

Abstract Objective Despite progress in treating relapsing multiple sclerosis (MS), effective inhibition of nonrelapsing progressive MS is an urgent, unmet, clinical need. Animal models of MS, such as experimental autoimmune encephalomyelitis (EAE), provide valuable tools to examine the mechanisms contributing to disease and may be important for developing rational therapeutic approaches for treatment of progressive MS. It has been suggested that myelin oligodendrocyte glycoprotein (MOG) peptide residues 35‐55 (MOG35‐55)‐induced EAE in nonobese diabetic (NOD) mice resembles secondary progressive MS. The objective was to determine whether the published data merits such claims. Methods Induction and monitoring of EAE in NOD mice and literature review. Results It is evident that the NOD mouse model lacks validity as a progressive MS model as the individual course seems to be an asynchronous, relapsing‐remitting neurodegenerative disease, characterized by increasingly poor recovery from relapse. The seemingly progressive course seen in group means of clinical score is an artifact of data handling and interpretation. Interpretation Although MOG35‐55‐induced EAE in NOD mice may provide some clues about approaches to block neurodegeneration associated with the inflammatory penumbra as lesions form, it should not be used to justify trials in people with nonactive, progressive MS. This adds further support to the view that drug studies in animals should universally adopt transparent raw data deposition as part of the publication process, such that claims can adequately be interrogated. This transparency is important if animal‐based science is to remain a credible part of translational research in MS.