Technotes

Technotes

Multiple Sclerosis

Introduction


Multiple sclerosis (MS), also known as disseminated sclerosis, is an autoimmune condition with demyelination of central nerves often resulting in physical and cognitive disabilities in many patients. It has a prevalence of 2 to 150 per 100,000 in the population, usually occurring in young adults and females.

Several disease-modifying treatments are currently available in diff erent countries, including: Avonex and Rebif (interferon beta1a), Betaseron or Betaferon (interferon beta-1b), Copaxone (polypeptide Glatiramer acetate), Mitoxantrone (immunosuppressant) and Natalizumab (humanized monoclonal antibody).

For several decades, rodent experimental autoimmune encephalomyelitis (EAE) has been broadly used as an important pharmacology model in new drug discovery and evaluation for MS. Mechanistic investigations on the immunopathogenesis of the demyelinating process, in different EAE models, have greatly elucidated the responsible mechanisms for autoimmune-caused neurological tissue damage and concepts of diff erent therapeutic strategies.

PharmaLegacy Models and Research Tools



EAE Models

SJL mice

C57BL/6 mice

Lewis rats

 Antigen    Specifi city

PLP 139-151

MOG 35-55

MBP

 Disease Onset  and Recovery

Day 12-14,  no recovery

Day 12-14,  no recovery

Day 10-12,  recover within  6-8 days

 Disease Type

Relapsing-remitting

Chronic progression

Monophase progression

 Similarities to  Human Disease

Relapsing-remitting disease course with demyelination and axonal damage

Chronic-progressive disease course

with demyelination and axonal damage

T cell infl ammation and weak antibody response

 Utility

Two-episode diseas.

Ideal for studying the eff ects of immunotherapeutic agents and various treatment regimens.

Variable disease incidence and course with cytotoxic demyelination. Ideal for studying T cell, macrophage mediated demyelination, axonal injury in demyelinated plaques and demyelinating anti-MOG autoantibody response.

High reproducibility. The acute onset and spontaneous recovery resemble the exacerbation and remission seen in MS.

 Primary   Endpoints

EAE disease score, incidence, mortality, mean maximum disease score, group mean score, EAE onset and duration, body weight

 Additional  Endpoints

Histopathology, immunohistochemistry, hematology, cytokines / chemokine analysis, T cell proliferation, permeability of BBB