A new mechanism for BG-12?

Dehmel T, Döbert M, Pankratz S, Leussink VI, Hartung HP, Wiendl H, Kieseier BC. Monomethylfumarate reduces in vitro migration of mononuclear cells. Neurol Sci. 2014 Feb 7. [Epub ahead of print]

Migration of immunocompetent cells into the central nervous system represents a key event in the immunopathogenesis of multiple sclerosis (MS). Fumaric acid esters have recently been approved for patients with MS. Their mode of action is not fully understood so far. We analyzed the effect of monomethylfumarate (MMF), the immediate metabolite of dimethylfumarate, on migration of lymphocytes and macrophages. Peripheral blood mononuclear cells (PBMCs) were isolated from patients with MS and healthy donors. PBMCs were treated with MMF in vitro and their migratory capacity was studied in a Boyden chamber assay. In addition, expression of matrix metalloproteinases (MMPs), chemokine receptors, adhesion molecules, and molecules of the oxidative stress cascade was assessed. MMF decreased the migratory capacity of T lymphocytes, but not of macrophages. Lymphocytes as well as macrophages responded to MMF by the upregulation of oxidative stress molecules; however, no effect was seen on the expression of MMPs, chemokine receptors, and adhesion molecules. There was no difference in comparison with cells from healthy controls. MMF reduces the migratory activity of lymphocytes most likely by changing their activational state. This points to a potential novel mode of action differentiating this drug from other available immunotherapies.
How does tecfidera work? One of the first things that happens is that is broken down to other things and one of those things is monomethylfumerate and this study suggests it blocks migration of cells and so could work just like some of the other available DMTs. So it could be a different drug to the same route of action so which one do you choose?

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  • IF this is the case I would choose as follows:

    – the DMT with higher/better effects
    – the DMT which costs less
    – the DMT with less side effects
    – the DMT with additional positive effects
    – the DMT which is easier to apply

  • It seems every other day there is a new mechanism of action for BG12. Is there anything that it cannot due? Maybe it will establish eternal youth as well.

  • MouseDoctor2
    The issue here is BG – 12 and yet do you find it appropriate to be so obsessive and cynical against glatiramer acetate? Is there a personal conflict between you and Teva? Regardless of its mechanism – it works for many patients, isn't it?

    • Hey Anonymouse,
      No issues with TEVA, merely pointing out that if you believe the literature, there is almost nothing that GA doesn't do (as each flavour of the month appears), which if it was true would mean it ought to be the miracle cure for MS. Yet is only, at best moderately effective in a subset of MSers. Go figure, but I always say, if it works for you, keep doing what you're doing.

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