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

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.

Reduction in CD11c+microglia correlates with clinical progression in chronic experimental autoimmune demyelination

“…EAE progression appeared in 58% of female mice lacking p38α in CD11c + cells and ∼40% of WT mice both of which initially developed mild EAE. Similar progression of clinical symptoms around 30 dpi was reported in non-obese diabetic mice used as a model of EAE progression (Baker et al, 2019; Basso et al, 2008; Buonvicino et al, 2019; Encinas et al, 1999; Tanabe et al, 2019). Why EAE progression follows a 30 dpi pattern and what triggers progression in a fraction of animals with mild EAE remains to be investigated.…”

Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function

“…At the same time, even though attempts to represent a chronic disease course have been made [ 23 ], and mouse strains, such as Biozzi ABH [ 6 ] and A.SW [ 314 ], show a clinical development resembling progressive MS, most EAE models are not suited to mimic primary/secondary progressive pathology or general disease chronicity. For instance, EAE induction in non-obese diabetic (NOD) mice, often claimed to represent the clinical course of progressive MS, can be used to study some neurodegenerative aspects of the disease, but overall it lacks evidence as a valid chronic model [ 15 ]. Taken together, the need remains for novel experimental approaches that better model progressive and chronic MS.…”

Biological Sex As a Critical Variable in CD4+Effector T Cell Function in Preclinical Models of Multiple Sclerosis

“…It should be noted that Baker and colleagues presented data in which they considered the disease pattern of individual MOG -immunized NOD mice monitored over 60 days. Only a subset of these mice showed a progressive pattern of phenotype (10).…”