Contract Research – EAE
Experimental autoimmune encephalomyelitis (EAE) is the model most commonly used to study efficacy of potential drugs for treatment of multiple sclerosis (MS).
Because of its many similarities to MS, EAE is used to study pathogenesis of autoimmunity, CNS inflammation, demyelination, cell trafficking and tolerance induction.
EAE is characterized by paralysis (in some models the paralysis is remitting-relapsing), CNS inflammation and demyelination. EAE is mediated by myelin-specific CD4+ T cells, but CD8+ cells and B cells play a critical role in some models of EAE.
EAE can be induced in two ways:
- By immunizing animals with myelin-derived proteins or peptides
- By injecting animals with CD4+ T cells specific for myelin-derived peptides
EAE can be induced in many animal species, but mice and rats are most commonly used.
EAE Model Comparison
| Model | Duration of Model (days) | Duration of Drug Treatment (days) | Suitable for testing agents which affect: |
|---|---|---|---|
| MOG35-55/CFA-Induced EAE in C57BL/6 Mice | 20-30 | 20-30 |
|
| PLP139-151/CFA-Induced,Remitting-Relapsing EAE in SJL Mice | 30-40 | 30-40 (preventive) 20-30 (therapeutic) |
|
| Adoptive Transfer EAE in SJL Mice | 35-45 | 10-30 |
|
| Adoptive Transfer EAE in C57BL/6 Mice | 35-45 | 10-30 |
|
At Hooke Laboratories we run several models of EAE:
MOG35-55/CFA-Induced EAE in C57BL/6 Mice
This model is recommended as a first pass for testing of potential drugs for treatment of MS, even if the exact mode of action of the drug is not fully understood.
This is the shortest mouse model of EAE. It has a rather good predictive value for efficacy in MS.
Mice develop EAE 8-14 days after immunization with MOG35-55/CFA and stay chronically paralyzed for the duration of the experiment.
Treatment of mice with a potential therapeutic usually starts on the day of immunization (preventive treatment), giving the drug the best chance of working, regardless of when it may be active during the disease induction process. Treatment can also be initiated when a fraction of mice (10-20%) develop the first signs of EAE (semi-therapeutic treatment) or as each mouse develops first signs of EAE (therapeutic treatment).
Because mice in this model develop a chronic progressive form of the disease accompanied with axonal damage early on, very few therapies are effective if the treatment is initiated at the onset or peak of disease in this model of EAE. However, treatment initiated at the peak or during the chronic stage of the disease may be used to test efficacy of drugs with the potential to help neuronal regeneration.
This model is approximately 20 to 30 days long. Effects of therapy started at the time of immunization are usually clear after 15 to 20 days.
PLP139-151/CFA-Induced, Remitting-Relapsing EAE in SJL Mice
This model most strongly resembles the remitting-relapsing form of MS (the most common form of MS).
Mice develop first episode of paralysis 11-14 days after immunization and, similar to most MS patients, they fully or almost fully recover from this first wave of paralysis. After a disease-free period of 1-2 weeks, 50 to 100% of the mice develop a second wave of paralysis (relapse).
In this model, treatment can be started on the day of immunization to test the effects of the drug on development of the first wave of EAE (preventive treatment). Alternatively, treatment can be initiated at the onset of clinical signs of EAE, to test the effect of the treatment on the development of the second wave of paralysis (therapeutic treatment).
This model is approximately 30 to 40 days long.
Adoptive Transfer EAE in SJL Mice
This model is particularly suitable for testing drugs expected to affect cell trafficking. In our experience, it is a very sensitive therapeutic model of EAE.
In this model, one group of SJL mice (donor mice) is immunized with PLP139-151/CFA. Ten days later, spleens are isolated from the immunized mice and splenocytes are restimulated in vitro with PLP139-151 for 3 days to generate encephalitogenic T cells.
These encephalitogenic T cells are then injected into a new group of SJL mice (recipient mice). These recipient mice develop EAE 7-10 days after the cell transfer. Because fully encephalitogenic T cells are transferred into the recipient mice, this model can be considered therapeutic even if the drug is administered from the day of cell injection (6-7 days before disease onset).
To test a potential therapeutic reagent under more stringent conditions, treatment can be started several days after the cell transfer or even at the time of first clinical signs of EAE.
This model is approximately 45 days long, but drug treatment only starts 15 days or more after initiation of the experiment. The effects of the drug are usually clear 12 to 20 days after initiation of treatment.
Adoptive Transfer EAE in C57BL/6 Mice
This model is particularly suitable for testing drugs expected to affect cell trafficking, as well as therapeutics targeting Th17 cells. In our experience, it is a very sensitive therapeutic model of EAE.
In this model, one group of C57BL/6 mice (donor mice) is immunized with MOG35-55/CFA. After 11 days, spleens are isolated from the immunized mice and splenocytes are restimulated in vitro with MOG35-55, IL-12 and anti-IFNγ antibodies for 3 days to generate encephalitogenic T cells. The encephalitogenic T cells are injected into a new group of C57BL/6 mice (recipient mice). These recipient mice develop EAE 7 to 10 days after the cell transfer.
The encephalitogenic T cells generated in this model are a mix of cells having either Th1 or Th17 phenotypes, with a majority having the Th17 phenotype. While many past studies suggested that Th1 cells play a critical role in MS and EAE pathogenesis, more recent work has suggested that it is Th17 cells, rather than Th1 cells, which play this role. Because of the large number of Th17 cells, this model can be used to test therapeutics targeting Th17 cells.
Because fully encephalitogenic T cells are transferred into the recipient mice, this model is considered therapeutic even if the drug is administered from the day of cell injection (6-7 days before disease onset). To test a potential therapeutic reagent under more stringent conditions, treatment can be started several days after the cell transfer or even at the time of first clinical signs of EAE.
This model is approximately 45 days long, but drug treatment only starts 15 days or more after initiation of the experiment. The effects of the drug are usually clear 12 to 20 days after initiation of treatment.
_150px.jpg)