EAE is not a useful model

Behan PO, Chaudhuri A. EAE is not a useful model for demyelinating disease Multiple Sclerosis and Related Disorders (2014) 3, 565–574

Experimental allergic encephalomyelitis (EAE) is the commonest, readily induced,organ specific, autoimmune disorder of laboratory animals of its kind. It is an artificial disorder brought about by the
immunisation of susceptible animals with brain antigens in complete Freund’s adjuvant (CFA). Variations can be induced by altering the nature of the antigen and the conditions involving immunisation.Whilst it is often described as a demyelinating disease, in strict terms it is not, since
the primary pathologic process is not demyelination but rather an encephalomyelitis that is immunologically induced. Rather, the prototype demyelinating disease is multiple sclerosis and its
variants. In this paper, the central question we ask is whether the data gleaned from the EAE model contributes to our understanding of the pathological events in MS. Towards answering this,we describe the historical development of EAE and its hyperacute form, and discuss the findings studied extensively in the non-human primate which show that ordinary EAE is an exact model for ADEM in the human, and that the hyperacute form of EAE is represented by AHLE in the human.Additionally,
we shall comment on the latest research on new variants of EAE,and explain our opinion regarding the use of EAE models in research aiming to understand the pathogenesis of multiple sclerosis.

When the concept of this article was first touted with MSARDS, we were asked to write a counter paper. However, we did not want to read this paper before writing ours as we would spend our time trying to counter the comments. We had no desired to have to try an defend a point of view that we may not subscribe to, such that there are some rubbishy EAE studies. 

We could counter that there are loads of rubbishy MS studies and there have been about 62,000 papers on MS, 6 times that of EAE so what…. this is unimportant. The argument is made that EAE is an immune-mediated disease rather than a demyelinating disease. However EAE was made to model an autoimmune aetiology, if MS has no autoimmunity then it all falls down but we know for a fact that there is autoimmunity in MS…it may be a consequence rather than a cause, but autoimmunity is present. It is argued that EAE is more like acute disseminated encephalomyelitis (ADEM) in humans.  

The article starts by arguing that in MS there are no immune infiltrates compared to the many found in EAE. However to equate disease of many years that occur after death compared to a few weeks in animals is comparing apples with pears. It is naive to think that immune infiltrates are not part of the problem in MS. This can be seen using MRI, and are seem clearly in brain biospies and the importantly the response to immunotherapies where the majority have a mechanism that stops white cells entering the CNS clearly points a finger at the immune arm being involved in both MS as well as EAE.  

EAE is clearly not MS scientists and Neurologists need to acknowledge this fact.

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  • The immunological model EAE has produced many modestly effective drugs used for RRMS. This blog has highlighted many of the important EAE papers that may have an impact in MS. Is a new paradigm necessary for developing novel more effective drugs? Has this model run its course or is there still much to be learned from EAE?

    • There is a lot to be learned.

      Remember don't blame the model for the presence or absence of drugs,blame the process

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