Merits and complexities of modeling multiple sclerosis in non-human primates: implications for drug discovery

Area of Science:

• Neuroimmunology
• Translational Medicine
• Primate Models

Background:

• Current preclinical models for multiple sclerosis (MS) inadequately predict clinical success.
• Experimental autoimmune encephalomyelitis (EAE) in adolescent mice lacks human immune system complexity.
• A translational gap exists between animal models and human patient outcomes.

Purpose of the Study:

• To evaluate an experimental autoimmune encephalomyelitis (EAE) model in adult non-human primates.
• To determine if a conventionally-housed marmoset model can bridge the translational gap for MS research.
• To investigate a novel EAE model with pathological similarities to MS.

Main Methods:

• Utilizing adult common marmosets (Callithrix jacchus) in a conventionally-housed colony.
• Inducing experimental autoimmune encephalomyelitis (EAE) in marmosets.
• Analyzing the pathological similarities between the marmoset EAE model and human MS.

Main Results:

• The marmoset EAE model exhibits remarkable pathological similarity to human MS.
• MS-like pathology arises from interactions between effector memory T cells and γ1-herpesvirus (CalHV3)-infected B cells.
• A small subset of CalHV3-infected B cells (<0.05%) is implicated in chronic inflammatory demyelination.

Conclusions:

• An EAE model in adult, pathogen-educated marmosets offers enhanced translational relevance for MS.
• Targeting CalHV3-infected B cells may be a viable strategy to limit MS-like pathology.
• This primate model could improve the prediction of therapeutic efficacy for MS treatments.