Monday, 15 June 2015

The pain of working with animal models.

Kasarello K, Kwiatkowska-Patzer B, Lipkowski AW, Bardowski JK, Szczepankowska AK. Oral Administration of Lactococcus lactis Expressing Synthetic Genes of Myelin Antigens in Decreasing Experimental Autoimmune Encephalomyelitis in Rats.
Med Sci Monit. 2015 May 31;21:1587-1597.

Background Multiple sclerosis is a human autoimmunological disease that causes neurodegeneration. One of the potential ways to stop its development is induction of oral tolerance, whose effect lies in decreasing immune response to the fed antigen. It was shown in animal models that administration of specific epitopes of the three main myelin proteins - myelin oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP), and proteolipid protein (PLP) - results in induction of oral tolerance and suppression of disease symptoms. Use of bacterial cells to produce and deliver antigens to gut mucosa seems to be an attractive method for oral tolerance induction in treatment of diseases with autoimmune background. Material and Methods Synthetic genes of MOG35-55, MBP85-97, and PLP139-151 myelin epitopes were generated and cloned in Lactococcus lactis under a CcpA-regulated promoter. The tolerogenic effect of bacterial preparations was tested on experimental autoimmune encephalomyelitis, which is the animal model of MS. EAE was induced in rats by intradermal injection of guinea pig spinal cord homogenate into hind paws. Results Rats were administered preparations containing whole-cell lysates of L. lactis producing myelin antigens using different feeding schemes. Our study demonstrates that 20-fold, but not 4-fold, intragastric administration of autoantigen-expressing L. lactis cells under specific conditions reduces the clinical symptoms of EAE in rats. Conclusions The present study evaluated the use of myelin antigens produced in L. lactis in inhibiting the onset of experimental autoimmune encephalomyelitis in rats. Obtained results indicate that application of such recombinant cells can be an attractive method of oral tolerance induction.


What's this all about? Its about trying to turn the immune response off. Is this interesting well maybe but this is not the reason it caught my eye. 

Central to the concept of the New EU regulations on the the use of animals in research is the concept of that the 3Rs (reduction, refinement and replacement) of animals in research is central to use of animals. 

This project is in need of a bit of 3Rs (e.g refinement) can you spot it?

No...so if I told you the substances used to induce EAE can cause swelling and if I told you injecting fluid into the skin, not below it (subcutaneous) where there is space to take fluid, but into it (intradermal). Any ideas.

OK now to give you an idea you have to put this mix into the ball of your foot, which is going to swell.

Yep I guess you may think this is unpleasant and you would be right. 

This process has been banned in the UK for well over twenty five years...this is because there are less painful ways to do this aim of getting EAE in rats.

So would I accept this....The UK often leads the way concerning animal research and other countries follow such as the rules that came into force in 2010 and had to be implemented by 2013 were in place in 1986 in the UK. I would write that there are alternatives and then I would say that the editor needs to take ethical advice 

Indeed I did this recently for another practise that has been banned in the UK.......The British journal rejected the paper.........

However, it shows that different countries have different sensitivities when it comes to animal research and in some countries/some peoples minds we are monsters if we do any animal research. 

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