At last…How to get relapsing progressive EAE made simple

Al-Izki S, Pryce G, O’Neill JK, Butter C, Giovannoni G, Amor S, Baker D. Practical guide to the induction of relapsing progressive experimental autoimmune encephalomyelitis in the Biozzi ABH mouse. Mult Scler Relat Disord. 2012 ;1:29-38.

Biozzi ABH mice develop a reproducible, relapsing-remitting form of experimental autoimmune encephalomyelitis (EAE) that becomes secondary progressive with disease duration. The relapses observed are T-cell dependent and can be inhibited by immune tolerance induction. In contrast the progressive neurodegeneration is T cell-independent and continues despite the re-induction of immune tolerance. Here we present a practical guide to EAE induction in the ABH mouse and approaches used to control relapses such that both autoimmune-independent and autoimmune-dependent mechanisms of neurodegeneration can be explored. Disease-related weight changes are associated with blood-brain barrier dysfunction and clinical disease. A new method for detecting neurodegeneration is described along with new experimental details that will aid in the undertaking of studies in EAE in mice, with particularly emphasis on ABH mice.

To most of you reading the blog, you don’t care much about animal work, but you do care about finding treatments.

Animals are one way to do this as we showed with the phenytoin in optic neuritis study that has implications for progressive MSers.

However, it is a research blog, and it is our research blog, so we need to engage people in what we do.

Biozzi Mice is a strain of mice that we became custodians of and showed that is a mouse strain that is highly susceptible to relapsing autoimmunity and also has secondary progressive disease. The were bred by a Brazilian (Guido Biozzi) working in Paris, France to study the genetic regulation of the antibody response and the ABH strain made high levels of antibody (AB=antibody, H = High). This is one of the best mouse strains for drug hunting because disease is reproducible. However we have to remember it is just one individual

The ARRIVE guidelines (CLICK) is a guideline of how to report animal studies to increase transparency.

This paper is a working protocol of how to get an control relapsing progressive EAE, This explains what is done in relation to the ARRIVE guidelines. It explains how you can get rid of relapsing disease with two simple injections.

Much animal work is in need of this transparency, because animal studies consistently fail to translate anything useful to humans.

I am sorry to say some of it would not translate into animal benefit because the experiments lack enough internal quality control.

Whilst I will take stick for staying this in a public forum, the results are out there for everyone to see and it is supposed to be a constructive rather than a destructive comment.

Studies may spark an interest in science but it is often a false hope when it comes to treatment. ARRIVE Guideline number 19 asks what is the relevance to human use and so many studies uses doses that would so far exceed what is relevant to humans.

It is written in stone in Europe that people using animals need to embrace the principles of 3Rs of animal work. This is not readin, rightin and rithmatic or reuse reduce and recycle but Refinement (of protocols to minimise suffering), Reduction (In the number of animals used) and Replacement(Using non animal alternatives).

If we do not aim to work to high standards,in the not too distant future, ethical review committees make take the view that the ends do not justify the means.

This study was published years ago as soon as the ARRIVE guidelines came out but was invisible as MSARDS failed to be seen on Pubmed and so was invisible until last week.

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  • In a way I agree that the results in animal models are difficult to be reproduced in humans. But then if incur érticas issues: human guinea pigs for drug testing? Um … not think recently I read an article about possible "organoid" human in the case of a brain, created in laboratories by researchers from Vienna (MD correct me if I'm wrong) … Perhaps this would be a closer solution to reproduce what actually occurs in the human body … And very interesting to have a Brazilian involved in this study because unfortunately in Brazil Science is very little valued, who knows as well as studies in animal models the incentive to change Basic Science here in this country …

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