Sunday, 2 December 2018

Advent 2

A favourite mechanism of action(MOA) of the inventors was that Glatiramer acetate induced a GA reactive Th2 response.. 

Aharoni R, Teitelbaum D, Sela M, Arnon R.Copolymer 1 induces T cells of the T helper type 2 that crossreact with myelin basic protein and suppress experimental autoimmune encephalomyelitis.
Proc Natl Acad Sci U S A. 1997;94:10821-6



Sure enough this was found in MS, by the immunology big guns.
Duda PW, Schmied MC, Cook SL, Krieger JI, Hafler DA. Glatiramer acetate (Copaxone) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis. J Clin Invest. 2000 Apr;105(7):967-76.

Qin Y, Zhang DQ, Prat A, Pouly S, Antel J. Characterization of T cell lines derived from glatiramer-acetate-treated multiple sclerosis patients. J Neuroimmunol. 2000 Aug 1;108(1-2):201-6
Neuhaus O, Farina C, Yassouridis A, Wiendl H, Then Bergh F, Dose T, Wekerle H, Hohlfeld R. Multiple sclerosis: comparison of copolymer-1- reactive T cell lines from treated and untreated subjects reveals cytokine shift from T helper 1 to T helper 2 cells.
Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7452-7

Chen M, Gran B, Costello K, Johnson K, Martin R, Dhib-Jalbut S. Glatiramer acetate induces a Th2-biased response and crossreactivity with myelin basic protein in patients with MS.Mult Scler. 2001;7(4):209-19.
This MOA was of course before T regulatory cells came along and kind of says the Th2 idea was rather rubbish.

Why?

"Response to therapy" I answer. 


If GA produces a Th2 response, then as GA is only modestly effective  then it says the influence of driving a Th2 response is only going to be modest. You can't have it both ways.

Jee Y, Liu R, Bai XF, Campagnolo DI, Shi FD, Vollmer TL. Do Th2 cells mediate the effects of glatiramer acetate in experimental autoimmune encephalomyelitis?Int Immunol. 2006 Apr;18(4):537-44.

Then there are the studies in mice that lacks IL-4 and IL-10 and so don't make Th2 cells but GA still has activity in the beasties. So is it really Th2?





2 comments:

  1. Pleeeease tell us this isn't the 25 different MOA for GA advent calendar

    ReplyDelete
  2. What other treatment has 25 mechanisms of action? :-(

    ReplyDelete

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