Sunday, 31 July 2011

Exposing the Failure of EAE

You wrote “I would like someone to expose the greatest fraud in MS research - EAE and other mouse models that bear no resemblance to human MS……The complete failure to identify any effective treatments form this model is the biggest scandal/ fraud, unfortunately no one is prepared to rock the boat and own up to this”.

Do not kid yourself there are always people who are prepared to rock the boat and state their opinions about animal studies, notably EAE

There are more than 100 compounds of proven efficacy in EAE, and we believe that it is pointless to add anymore to this list” (Sriram & Steiner)

“It is now possible to conduct a Phase II trial for anti-inflammatory MS drug candidates within a few months…..it is not useful to pre-screen potentially effective drugs using the EAE model” (Ransohoff)

It is true that there are only a few treatments that were found to be active in EAE, which have been translated into new drugs for MS. However, it is wrong to say that there have been no treatments that have resulted from work in EAE. The new breed of MS drugs such as Tysabri and Gilenya have their foundation firmly rooted in ideas from EAE or other animal studies.

This is likely to increase as drugs are being targeted at common causes of disease that occur both in both animal models and human disease. Therefore although EAE is not MS, if used sensibly it can be used to address some questions that will lead to "tomorrows therapies". Indeed there would probably be no drugs for MS without animal studies, as they have been essential in providing the basis of knowledge and the tools that have been required to provide drugs for MS.

There is a constant, ever evolving debate about the relevance of animals in research. As times change, so do practices, including banning of animal research where it is no longer considered useful. As you probably know animal use for cosmetic testing has been banned for many years and this too has become the way of animal testing of food products. However, for many medical aspects, we are not yet at that stage. If all such animals studies were considered futile, then because of the great human and financial costs involved in under taking such work, it would not be supported and would not be undertaken.

All animal studies within the United Kingdom must go through an independent ethical review process and permission to undertake this work is controlled by UK Government, Home Office via the Animals (Scientific Procedures) Act. These panels have the power to stop work with animals and these processes involve debates about the merits of EAE with regard to the research and MS and justifications for each line of research must be made.

There are many reasons for this slow-development in translating drugs towards the clinic, and one aspect is that indeed human MS is more complex than the simple experiment using EAE. However, there are many other reasons for this slow progress Furthermore you must also appreciate that it takes 10-15 years to develop a drug from animal studies to get a drug suitable for human use. Many will fail not because they could not work, but because they will not be sufficiently safe.

Some people (EAEologists) study EAE because they are more interested in the disease mechanisms, rather than treating MS. Some "ThEAEologists" convince themselves that EAE is MS, without really ever understanding what MS is. We try to use our animal models in a context that is useful for MS and we are committed to the Refinement, Reduction and Replacement principles of animal use in research.

The public including MSers, scientists and clinicians continue to rock the boat, and we are not adverse to a bit of rocking ourselves.


Todays research is tomorrows progresss.

1 comment:

  1. 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.

    Abstract

    Orally administered laquinimod was found to be present within the central nervous system (CNS) in both healthy mice and mice with experimental autoimmune encephalomyelitis (EAE). Laquinimod inhibits development of both acute and chronic EAE. Furthermore, laquinimod minimizes inflammation, demyelination and axonal damage in MOG-induced EAE in mice treated at disease induction and following clinical disease onset.

    http://www.ncbi.nlm.nih.gov/pubmed/21429524

    And here is the reality today:

    Teva Pharmaceutical Industries Ltd. (TEVA)’s experimental multiple sclerosis pill failed to reduce relapses more than placebo in a clinical trial, dealing a blow to the company’s effort to find a successor to an older drug.

    “Laquinimod is dead, if not regulatorily, then commercially,”

    http://www.bloomberg.com/news/2011-08-01/teva-s-oral-multiple-sclerosis-drug-fails-to-meet-goal-of-clinical-trial.html

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