MS Models in Drug Discovery Studies

Multiple sclerosis (MS) is an autoimmune neuroinflammatory disease in which demyelination of the central nervous system (CNS) is a hallmark characteristic. There are four major disease categories that have varying degrees of progression and symptoms:

  • Relapsing-remitting MS (RRMS), which is characterized by flare-ups and remissions of symptoms
  • Secondary progressive MS (SPMS), which may develop in some relapsing-remitting MS patients and is characterized by worsening symptoms with no remissions
  • Primary progressive MS (PPMS), where the symptoms progressively get worse with no remissions 
  • Progressive-relapsing MS (PRMS), which has progressive symptoms from onset with occasional flare-ups

There is no curative therapy currently available for MS; however, a handful of drugs targeting the autoimmune component are used primarily to manage flare-ups. Recently, a new breakthrough therapy (ocrelizumab) was approved for primary progressive MS as well as relapsing-remitting MS, but there is still an unmet clinical need for the more debilitating forms of MS.

The need for more translational preclinical models of Multiple Sclerosis

Cover image of The need for more translational preclinical models of Multiple Sclerosis whitepaperThere is no curative therapy currently available for MS, but a handful of drugs targeting the autoimmune component are used primarily to manage flare-ups.

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Current MS Models

Preclinical studies in animal models typically take two avenues where one avenue focuses on the autoimmune component and the other avenue focuses on the mechanisms of demyelination independent of the autoimmune effects. The EAE (experimental autoimmune encephalomyelitis) series of MS models are widely used to test therapies targeting the inflammation component of MS, while MS models where demyelination is induced by cuprizone, lysolecithin, or ethidium bromide are increasingly being used to test therapeutic candidates.

Charles River conducts studies in both inflammation and demyelination models of MS to test the efficacy of novel therapeutics. Interested in learning about other MS animal models?

Demyelination MS Models

Charles River offers cuprizone- and lysolecithin-induced rodent models of demyelination to test novel therapies for MS. The cuprizone model uses a validated study design where demyelination is induced followed by a recovery period of remyelination. During the study, motor performance using rotarod tests or fine motor kinematic analysis, anxiety, and cognition are measured at specific intervals along with confirmation histology and IHC studies. Studies using large animal EAE models include MRI analysis and pathological assessment of lesions.

Inflammation Models

EAE ms models are considered to be standard models for brain inflammation and demyelination studies. At Charles River, validated rat and mouse models of EAE are available for validation studies to test novel MS therapies. The following EAE models are available:

  • MOG35-55 EAE in C57BL/6 mice
  • SCH EAE in rats
  • MOG1-125 EAE in Dark Agouti rats

These MS mouse models have been validated with positive control compounds and drugs including dexamethasone, glatiramer acetate, and fingolimod. The EAE models are used to monitor disease progression and therapeutic response using the following assays:

  • Spinal cord and brain pathology monitored via histological techniques and ELISA assays
  • SPECT/CT monitoring of inflammation in the brain and spinal cord
  • Flow cytometry-based immunophenotyping of peripheral and central nervous system tissues

MS Models Validation Frequently Asked Questions