If people are working with animals, especially those of a severe nature, then is it time to change!
In this report we suggest that what people are calling progressive EAE is nothing more that relapsing-remitting EAE that is ascychronous with increasing poor recovery. This is important because we know that relapsing EAE responds to T cell therapy but we want alternative treatements for progressive MS. If the model is not used in a way that is fit for purpose then, you are not going to find treatments and the chances of the drugs, based on these models, working are less likely.
Some people will be annoyed that we are suggesting that there is bad data handling and interpreation as these types of studies are being published in Nature, PeeNAS and the lemmings are following. However others are following in this bad practise. Time to change and show your data, we can then analyse it and work out if you are reporting gold dust or dirty underwear (pants).
This post is bigger than MS as it makes a fundemental point, so Tweet, email and share
I say prove us wrong and show the raw data. In five minutes we would know if we need to eat humble pie or say this study is flawed. If the high Impact journals start to do this, I predict we would see alot of EAE papers crumble. They don’t pass the “Smack you in the eye test”
It is time to change. Our University has created space where raw data can be depositied, but I suggest a spead sheet with the paper is what is needed. Then we don’t have to beg to get the data as despite statements saying data is available, many authors do not comply with these hollow practises.
Autoimmune encephalomyelitis in NOD mice is not initially a progressive multiple sclerosis model. Baker D, Nutma E, O’Shea H, Cooke A, Orian JM, Amor S.Ann Clin Transl Neurol. 2019 Aug;6(8):1362-1372.
OBJECTIVE:Despite progress in treating relapsing multiple sclerosis (MS), effective inhibition of nonrelapsing progressive MS is an urgent, unmet, clinical need. Animal models of MS, such as experimental autoimmune encephalomyelitis (EAE), provide valuable tools to examine the mechanisms contributing to disease and may be important for developing rational therapeutic approaches for treatment of progressive MS. It has been suggested that myelin oligodendrocyte glycoprotein (MOG) peptide residues 35-55 (MOG35-55 )-induced EAE in nonobese diabetic (NOD) mice resembles secondary progressive MS. The objective was to determine whether the published data merits such claims.
METHODS:Induction and monitoring of EAE in NOD mice and literature review.
RESULTS:It is evident that the NOD mouse model lacks validity as a progressive MS model as the individual course seems to be an asynchronous, relapsing-remitting neurodegenerative disease, characterized by increasingly poor recovery from relapse. The seemingly progressive course seen in group means of clinical score is an artifact of data handling and interpretation.
INTERPRETATION: Although MOG35-55 -induced EAE in NOD mice may provide some clues about approaches to block neurodegeneration associated with the inflammatory penumbra as lesions form, it should not be used to justify trials in people with nonactive, progressive MS. This adds further support to the view that drug studies in animals should universally adopt transparent raw data deposition as part of the publication process, such that claims can adequately be interrogated. This transparency is important if animal-based science is to remain a credible part of translational research in MS.
The MS Societies should insist that this is a common practise of future grants they fund. Don’t do it and funds should be withdrawn. That way change occurs and it improves animal science.
The 3Rs are part of European Law and this move towards transparency means that meaningless or poor quality science will not have to be reproduced to show it is bad, you can use the authors own data to do this.
Check the output retrospectively to see it is done, if not no further cash!
If you are supporting this type of work..thank you for supporting animal research but you should demand that there is transparency
In the review, it was questioned if the difference we saw verses others was a lab thing, sure it is possible, but is unlikely. This is why we requested permission to reproduce a figure from a paper from a lab claiming progressive EAE. The author hangs themselves, so I am sure it is not a lab variation thing.
However go on prove me wrong “Show us the Data”
P.S. No new animals were used for this study it came from historical studies