Summary: EAE models aspects of autoimmunity, inflammation, demyelination, cell trafficking and tolerance induction seen in Multiple Sclerosis.
Model Description
Experimental autoimmune encephalomyelitis (EAE) is the most commonly used model for the preclinical development of drug candidates for treatment of optic neuritis and multiple sclerosis (MS).
As the EAE model models aspects of autoimmunity, inflammation, demyelination, cell trafficking and tolerance induction seen in MS, it provides a versatile tool for a broad array of drug candidates.
The model is characterized by paralysis, CNS inflammation and demyelination. We are using MOG35-55 antigen to induce a phenotype reminiscent of MS with a well-defined onset of development of EAE and EAE severity. In addition, the EAE model mimics aspects of optic neuritis and demyelination of the optic nerve.
Animal species | Mice (C57BL/6) |
Method of induction | – MOG35-55/mL emulsion – Killed mycobacterium tuberculosis H37Ra/mL emulsion – Pertussis toxin (PTX) |
Follow-up period | Up to 28 days |
Route of compound administration | Topical, systemic, intravitreal, intravenous (infusion) |
Read-outs | Standard readouts: – Behavioral analysis and scoring – Infiltration of cervical spinal cord – Assessment of demyelination Optional: – Assessment of functional vision by electroretinogram and visually-evoked potentials – Infiltration of optic nerve and assessment of demyelination – Unbiased estimation of the total number of retinal ganglion cells (stereology) |
Outcomes and Read-Outs
Scoring of behavioral phenotype
References
- Gran B, Zhang GX, Yu S, Li J, Chen XH, Ventura ES, Kamoun M, Rostami A. (2002). IL-12p35-deficient mice are susceptible to experimental autoimmune encephalomyelitis: evidence for redundancy in the IL-12 system in the induction of central nervous system autoimmune demyelination. J. Immunol. 169, 7104–7110.
- Lo AC, Saab CY, Black JA, Waxman SG. (2003). Phenytoin protects spinal cord axons and preserves axonal conduction and neurological function in a model of neuroinflammation in vivo. J Neurophysiol. 90(5):3566-71.
- Tenhunen A. Refinement strategies in pharmacologic efficacy models. Experimentica’s Youtube channel, 2020.