Anti-migration effect of DMF: alarms bells start ringing

This study looks at the influence of dimethyl fumarate (DMF) and its active breakdown product on control of the blood brain barrier

Breuer et al. Dual action by fumaric acid esters synergistically reduces adhesion to human endothelium.

In this study, they looked at the effect of cells from people treated with DMF, on whether they cross blood vessel cells in tissue culture. They found that it reduced expression of migration marker on the blood vessel and a different one on the white blood cell. 

So it is saying it can work like natalizumab.

Should you be worried? 

We know natalizumab is very effective, but we also know that DMF is not in the same league at natalizumab when it comes to disease inhibition. This says to me that it can’t be that good at blocking the migration, but it may contribute to the activity.

However, you have to be careful what you wish for because, if you look at drugs that block migration of white blood cells, you would get rebound disease, as seen with natalizumab and perhaps fingolimod, when you stop DMF.

However, the fact that DMF does not always block rebound due to natalizumab, suggests that this mechanism is not the main issue. So not much to worry about.

Another property of DMF is that when you stop treatment the white blood cells do not come back. We need to understand this, to work out if we need to be concerned.

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  • What does this mean if your switching from DMF to Alemtuzimab? I as told to stop DMF for 2 months but was treated earlier after cancellation. Meaning was only off DMF for 4 weeks. Is this likely to cause a problem? However was on DMF for 1 and half years.

  • The concern would be of you do not repopulate, but if you have had alemtuzumab it will deplete what was left and then hopefully you repopulate as normal and there is nothing to worry about. Likewise the swift treatment means your ms was unlikely to reactivate. I have seen examples of people with low blood counts on DMF that repopulate fine. You could ask to see your blood counts. If low you will be at risk of infection.If you look at our paper in JAMA neurology you can see expected white cell counts or look at other Cambridge studies.

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