Multiple Sclerosis/EAE


Clinical Background

Multiple sclerosis (MS) is a chronic disease that results in the progressive loss of neurological function through the destruction of the myelin in the central nervous system. The destruction of myelin reduces and ultimately eliminates the ability of nerve cells within the brain and spinal cord to communicate with each other. Due to the broad based nature of the attack upon the immune system, almost all neurological symptoms can appear as part of the disease, including physical and cognitive disability, as well as neuropsychiatric disorders. Many victims of MS experience a relapsing-remitting form of the disease in which partial or complete recovery occurs between attacks. MS is generally thought to be a form of autoimmune disease, although no auto-antigen has been described, and many treatments for MS are drugs that suppress the immune system.

Preclinical Model

Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model of MS. EAE is induced by immunizing animals with myelin, either from spinal cord homogenates, purified myelin proteins or in the form of peptides based on specific epitopes of myelin proteins. Once immunized with the appropriate peptide and adjuvant, animals develop either an acute episode of disease, or a chronic progressive form of the disease. The progression of the disease is evaluated and scored with a 5 point scoring scale that evaluates muscle tone in the tail and limbs.

Preclinical Models

Model Description Length Endpoints
Chronic EAE
Myelin oligodendrocyte glycoprotein (MOG) is administered resulting in loss of muscletone 30 days EAE score, histology
Relapsing EAE
Proteolipid protein (PLP) is administered resulting in relapsing EAE symptoms 40 – 50 days EAE score, histology

 

Chronic EAE Induced by MOG

EAE is induced by administration of myelin oligodendrocyte glycoprotein (MOG) emulsified in Complete Freund Adjuvant (CFA). Pertussis toxin is also administered to the animals in order to facilitate immune cell access across the blood-brain barrier. The result is a complete loss of muscle tone in the tail and impaired function of the hind limbs. This loss is present by day 12 and lasts until study completion. Treatment with prednisolone protects against the development of EAE and can be included as a positive control in study design.

Mean EAE Score

 

Relapsing EAE Induced by PLP

Many MS patients experience relapsing bouts of disease in between partial or complete remissions. Relapsing EAE can be induced by administration of proteolipid protein (PLP). The result is an acute bout of loss in muscle tone followed by a relapse in symptoms. Relapsing is defined as an increase of at least one grade in clinical score for at least two consecutive days after remission.

Relasping EAE Induced by PLP

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Relasping EAE Induced by PLP

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Slide1

*Cross sections of the spinal cord (5 micron) stained with Luxol Fast Blue and counterstained with Periodic acid-Schiff (PAS) stain. On the left is a representative photograph of a section taken from a mouse treated with PLP. One the right is a representative photograph of a section taken from a control mouse. Arrows highlight areas of depleted myelin.