Failure to translate

Baker D & Amor S. Experimental autoimmune encephalomyelitis is a good model of multiple sclerosis if used wisely. MSARD Epub

Although multiple sclerosis is a uniquely human disease, many pathological features can be induced in experimental autoimmune encephalomyelitis (EAE) models following induction of central nervous system-directed autoimmunity. Whilst it is an imperfect set of models, EAE can be used to identify pathogenic mechanisms and therapeutics. However, the failure to translate many treatments from EAE into human benefit has led some to question the validity of the EAE model. Whilst differences in biology between humans and other species may account for this, it is suggested here that the failure to translate may be considerably influenced by human activity. Basic science contributes to failings in aspects of experimental design and over-interpretation of results and lack of transparency and reproducibility of the studies. Importantly issues in trial design by neurologists and other actions of the pharmaceutical industry destine therapeutics to failure and terminate basic science projects. However animal, particularly mechanism-orientated, studies have increasingly identified useful treatments and provided mechanistic ideas on which most hypothesis-led clinical research is based. Without EAE and other animal studies, clinical investigations will continue to be “look-see” exercises, which will most likely provide more misses than hits and will fail the people with MS that they aim to serve.
There is an increasing set of people criticising animal studies, but the failure to deliver drugs for MS may have as much to do with human activity as problems with the animals. Whilst many neurologists have been happy to bash animal studies for many years, it is important that they too become self critical so that they can take their share of responsibility in the failure to translate.
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Potential Reasons or Failures in the Drug Development Process
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Basic (Pre-clinical) Science
Pharmaceutical Science
Clinical Science
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Can you come up with examples for eachpoint...I can.

CoI Members of Team G are authors of this paper.

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