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Another failure in MS and the EAE-bashers are out

Following the sad news that a new trial laquinimod had just failed to show a significant effect in MS.

The first post is: ” Anonymous said… Another EAE failure:”

“Here is a wonderfully optimistic paper on how laquinimod healed mice: Insight into the mechanism of laquinimod action. Brück W, Wegner C”.

First remember that laquinimod has already been shown to have a positive effect in one major trial and this new trial just failed to meet its primary aim, this does not mean it had no effect!

OK the paper you mention is bouyant, but let’s take a look at what the EAE papers were actually saying. Yes Wegner showed there was a good effect in their EAE study

However the good effect was at 25mg drug per kg of body weight but at 5mg/kg the effect was marginal. In another study the effects below 2mg/kg were not very compelling, Therefore EAE studies show that the drug works (at least has some effect) at doses above 2mg/kg but not below. Mice however break down drugs much more quickly after delivery than humans. Therefore it takes about 10 times more drug to get an effect in mice than in humans?

However let’s see what they did in the trial. They gave a daily pill of about 0.6mg. This is equivalent to about 0.001mg/kg. So even taking the ten-times scaling factor to go from mouse to man, then this dose is still way short of the active doses used in animals. Therefore, is it a surprise that the drug did not do as well in MS as it could do in EAE?

Often there are reasons why you can not use such big doses in humans, usually due to side-effects that are not an isssue in the EAE studies

So don’t always knock the animal, but how the knowledge from them is implemented!

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