Friday, 7 November 2014

Intrathecal depletion of B cells

Lehmann-Horn K, Kinzel S, Feldmann L, Radelfahr F, Hemmer B, Traffehn S, Bernard CC, Stadelmann C, Brück W, Weber MS. Intrathecal anti-CD20 efficiently depletes meningeal B cells in CNS autoimmunity. Ann Clin Transl Neurol. 2014 Jul;1(7):490-6.

Clinical trials revealed that systemic administration of B-cell-depleting anti-CD20 antibodies can hold lesion formation in the early relapsing-remitting phase of multiple sclerosis (MS). Throughout the secondary-progressive (SP) course of MS, pathogenic B cells may, however, progressively replicate within the central nervous system (CNS) itself, which is largely inaccessible to systemic anti-CD20 treatment. Utilizing the mouse MS model of experimental autoimmune encephalomyelitis, we show that intrathecal (i.t.) administration of anti-CD20 alone very efficiently depletes meningeal B cells from established CNS lesions. In SP-MS patients, adding i.t. administration of anti-CD20 to its systemic use may be a valuable strategy to target pathogenic B-cell function.


Rituzimab had a positive effect on relapsing progressive MSers. This could suggest that (a) only the response that drives relapsing MS responds to drug treatment and what drives progressive MS is different (b) The antibody depletes the B cells in the periphery and can get into the CNS whilst the blood brain barrier is compromised  and so deals with the problem of MS. So for people without blood brain barrier dysfunction the antibody does not get in to the brain and can't kill the B cells. Some people argue it is that it is the presence of B cells in the CNS that is the problem with progressive MS. 

So the solution could be inject the antibody into the brain, kill the B cells and that's the end of progressive MS. So in this study they inject anti-B cell antibodies into the brain and if they select the right type of antibody then they can show it can kill B cells.

However intrathecal anti-B cell antibodies are, I think, already ongoing in progressive MS, so should we be concerned with this in animal models of MS? Will it work? Lets hope so. 

However we can ask has this experiment been done. The answer is maybe. There are B cell-depleting agents that get into the CNS, like cyclophosphamide and clabribine but did they work in progressive MS? For cladribine the trials said no. However was the optimum dose used for B cell depletion in the CNS?. It was probably never looked at.

5 comments:

  1. MD,

    Is there any known link between the microglial cells thought to be active in progressive MS and activity of these CNS B cells?

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  2. So anti-CD20 removes B-cells ... isn't that what it's supposed to do?
    I don't understand why this study was needed or what it proves

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  3. This post from September was about intrathecal rituximab administration
    http://multiple-sclerosis-research.blogspot.com/2014/09/depleting-b-cells-in-cns.html

    It said "Peripheral CD20+ B cells were reduced, while oligoclonal bands were unaffected"

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  4. This research seems really important ie potentially a treatment for progressive MS. Has the focus on t cells been wrong? Can prof g give us an idea of when we might here from some of the b cell depleting trials?

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