Clinical trials the good the bad and the really bad

Ransohoff RM. Animal models of multiple sclerosis: the good, the bad and the bottom line. Nat Neurosci. 2012  26;15(8):1074-7. 


Multiple sclerosis (MS) is a spontaneous, acquired, inflammatory demyelinating disease of the human CNS. Because it involves a complex interaction between two of the most intricate biological systems, immune system and CNS, animal modelling has been critical for addressing MS pathogenesis. MS models were originally developed serendipitously more than 75 years ago. Immune-mediated, toxic, viral and genetic models of demyelination are now used to understand the manifold aspects of MS. MS treatments evolved in part from animal model research, and further progress is envisaged in large part because these systems have been continually refined and their use focused on questions whose relevance was established by studying the human disease.


This is a review and I do not normally comment on reviews as they tell you little new things.

Richard Ransohoff has been quite critical of EAE in the past 

"It is now possible to conduct a Phase II trial for anti-inflammatory MS drug candidates within only a few months, using magnetic resonance imaging. This approach is effective at discarding useless drugs, identifying successful treatments and for highlighting safety concerns quickly. Given the availability of this technology, it is not useful to pre-screen potentially effective drugs using the EAE model. Drug development should not be hindered by an outlook that advocates testing each compound in the EAE system before proceeding".


However having being part of studies on a few recent EAE papers he has changed his view?:-)

In this current article he writes "EAE nevertheless has unequivocal value as a model of the inflammatory aspects of MS and can be regarded as an essential tool in the armamentarium of the MS researcher"


However, he then states a number of deficiencies in EAE. Unfortunately many things stated as fact are far from the reality. More reading was warranted. However my thoughts will fall on deaf ears and the harm is done........So another nail in the beasties coffin.

It is all well and dandy for clinicians to slag off EAE work, but sometimes self-reflection is needed to see their part in the downfall of so many drugs.



One day I may write an article "Clinical research the good the bad and the really bad" I wonder if Nature Neuroscience would publish that....... I suspect not. 

We know there is some really bad as you get to see it here, but there is worse we do not post on.

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