As a card carrying EAEer I understand the view that studies in animal studies give the basis for benefit in controlling MS. Indeed this is the basis for many animal studies.
Aliyu M, Saboor-Yaraghi AA, Sahraian MA, Noorbakhsh F.. The Experimental Autoimmune Encephalomyelitis (EAE) Model: A Gateway to Successful Translation of Multiple Sclerosis Therapies.
The study talks about the concept of 4Rs. “The traditional 3R principle—Replacement, Reduction, and Refinement—have limitations in guiding the ethical management of animal experimentation, conducting animal studies, and utilizing animal-derived materials. To address these gaps, the field has introduced the 4R principles, which expand the original framework by adding “Responsibility.” The Responsibility principle highlights the ethical obligation of researchers to consider the welfare of experimental animals during all procedures. It calls for researchers to take accountability for their actions and decisions, ensuring that they actively protect animal welfare and exhibit empathy across species” (Liu J et al. Front Pharmacol. 2025; 16:1543316). The authors of the current paper indicate that “The EAE model serves as a critical platform for bridging this gap and offers valuable insights into the complex interplay between immune-mediated inflammation and neurodegeneration.”…..I sort of agree with the view as some people ask for EAE data before thinking of moving forward…However I would rather describe it as a “crutch”…that helps to support some people to take the plunge into a human trial. A positive study in EAE gives solice…however the animal studies are seldom done in a way that the therapeutics are ultimately used in humans..Furthermore
They say “One notable example of an effective therapeutic intervention is the use of monoclonal antibodies that target specific immune pathways. For instance, anti-CD4 monoclonal antibodies have been shown to significantly reduce disease severity in EAE models by inhibiting T-cell activation and preventing their infiltration into the CNS. This finding underscores the value of the EAE model as a powerful tool for assessing the preclinical efficacy of emerging therapies designed to modulate immune responses”.
This where I say “hang on a minute” CD4-depleting antibody therapy was considered to be a failure in MS and whilst it is suggested that EAE was the translational tool that allowed drug development, I am not so sure. To translate you have to start with success in animal studies and then move to humans…however in most cases it was started with a positive result in humans and then people do the experiment in animals afterwards. This backwards translation….Beta interferon was the first drug to work in MS. Beta interferon is species specific and so human beta interferon does not work in mice…shame some EAEers didn’t know this fact then they inhibited EAE with human beta interferon.
Glatiramer acetate came next and was first shown to work in animals before humans, but you need to do experiments in certain ways to get it to work. Natalizumab has its origins in animals too. However teriflunomide is the metabolite of leflunomide which works in arthritis and anti-CD20 had origins of working in arthritis, dimethyl fumarate was being used for psoriasis when it was discovered that it inhibited MS, sphingosine-1-phosphate modulators was used in transplantation. CD52 was used in humans before it was used in EAE…..
Yes there are limitations in the use of EAE but I believe it can show principles and biology that can translate….but don’t blame the animals when there is failure in a human trial there are many reasons why animal study results do not show success in human trials.
COI None
Disclaimer. My views alone
Source: multiple-sclerosis-research.org