New Scale May Better Assess MS Changes, Therapy Response in Mice

A new scoring system might more precisely evaluate disease development, severity, and treatment response in a commonly used mouse model of multiple sclerosis (MS) known as the experimental autoimmune encephalomyelitis or EAE model, scientists report.

This scoring system, called “I AM D EAE,” was described in the study, “The innovative animal monitoring device for experimental autoimmune encephalomyelitis (“I AM D EAE”): A more detailed evaluation for improved results,” published in Multiple Sclerosis and Related Disorders.

Experimental autoimmune encephalomyelitis is a laboratory-induced mouse disease that is the most commonly used to model MS in mice. Many approved therapies showed early success in EAE models, highlighting its utility as a platform for testing potential treatments before bringing them into a clinical trial.

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With EAE mice, researchers commonly use numeric scales to score the severity of the disease based on measurable symptoms. Most commonly, mice are scored on a simple scale from zero (no detectable abnormalities) to five (dead or dying). However, such ratings can be imprecise and subjective.

“Even though most scoring scales are similar, some of them present variations that might affect the clinical score and the comparison between experiments. Moreover, most of the scales are relatively simple and do not always correlate to the signs each animal shows,” the researchers wrote.

“Thus, the final score given to an animal depends, to some extent, on the subjective interpretation of the evaluator. As a result, animals with different clinical signs can be assigned the same score or animals with similar clinical signs can be scored differently,” they added.

A team of scientists in Spain and Portugal set out to create a novel scoring system for EAE that could more precisely capture how the disease manifests in mice.

“The aim of our work was to develop a more precise scale, less subjective and that could also be used by non-expert researchers,” the scientists wrote.

Their scale, called I AM D EAE, assesses symptoms across nine domains, with each domain given specific numerical weights. For example, if the end of the mouse’s tail is limp and droopy, this symptom is scored for 0.5 points. If the whole tail is affected, it’s scored for .85 points. Another 0.15 points is added if the tail sticks to the floor when the mouse is standing.

Other domains assess limb function. Here, if one hind leg is partly dragging or flapping, it’s scored 0.5 points, while both legs dragging is scored 1 point. If one leg is completely paralyzed, it scores 1 point; both hind legs being paralyzed score 1.75 points.

Abnormal mice behaviors like limited exploration and movements like staggering also are included in some of the domains.

These domains add up to a total possible score of five, in keeping with the scoring systems already in wide use.

To test their system, three scientists used I AM D EAE to score several affected mice; a standard 0–5 scale also was used for comparison. Results showed that the scientists’ scores on the new measure aligned well with each other, and also with scores on the standard scale.

“The ‘I AM D EAE’ system is composed of different items, and researchers evaluate each of them independently and assign the corresponding score,” the researchers concluded. “Remarkably, the final score is more detailed and, therefore, more diverse but, as shown, it significantly correlates to the commonly applied scoring system.”

The team added that the new system “is a robust tool, and it efficiently captures disease evolution at all stages. In this way, animals scored with our new system could be compared to previously published works and, at the same time, particular aspects of the model can be further investigated.”