Tolerance to myelin peptides in MS

T

Is the idea of intravenous tolerance an approach that can work in MS. It has been done. Here is an example. The nine people below had MS and were given a cocktail of intravenous myelin peptides stuck onto white blood cells as we had done in the mice. Did their MS disappear…The answer was no…at least not for some of them as those results have been published elsewhwere (Lutterottti et al. 2013). So are the peptides the wrong targets? or was it because they didn’t deplete the T cells first?. The original supporting patent was filed in about 2007 and so time has probably ticked on this one (You only get about 20 years to develop your treatment and recoup your costs). I suspect the years of preclinical work done by the inventors and other people made the patent have more holes in it than a piece of Swiss cheese Such that if it worked the patent would be discredited as lacking inventiveness in the approach and choice of antigens selected and perhaps explaining why pharma have not developed it yet. But hey what do I know, this is only an idea

The peptides were selected based on T cell responses and these could be reduced by tolerance induction, here they looked at antibodies. As you can see the antibody responses to Rubella (German Measles), EBNA1 (EBV) and Cytomegalovirus (CMV) were un- affected but the antiboody body responses dropped in one of the 9 individuals who have antibodies to the myelin peptides. So it supports our earlier tolerance studies, However, that all these people had MS but most did not have an antibody response to the myelin peptides shows that they are not centrally important to MS, or they would have been present in all. The antibody response to whole myelin basic protein was not affected suggesting that people respond to other myelin basic protein peptides. However, if you can deliver proteins in a way that does not switch the immune response on you may have a way to stop autoimmunity. All you need to know are which proteins are important to target.

Peschl P, Reindl M, Schanda K, Sospedra M, Martin R, Lutterotti A. Antibody responses following induction of antigen-specific tolerance with antigen-coupled cells. Mult Scler. 2015;21(5):651-5

We have recently demonstrated the safety and tolerability of a novel therapeutic regimen employing autologous blood cells chemically coupled with seven myelin peptides to induce antigen-specific tolerance in MS (ETIMS study). The aim of the current study was an extended safety analysis to assess the effect of the ETIMS approach on antibodies to common autoantigens, the myelin peptides used and common recall antigens. None of the patients showed induction of autoantibody responses. One patient had a measurable myelin peptide-specific response at baseline, which was reduced after treatment. Total immunoglobulins and recall antibody responses showed no significant change.

About the author

MouseDoctor

Add comment

By MouseDoctor

Translate

Categories

Recent Posts

Recent Comments

Archives