Effects of glatiramer acetate in a spontaneous model of autoimmune neuroinflammation

Am J Pathol. 2014 Jul;184(7):2056-65. doi: 10.1016/j.ajpath.2014.03.009. Epub 2014 May 9.


Glatiramer acetate (GA) (Copaxone), a well-established drug for the treatment of multiple sclerosis, is believed to modulate numerous pathways including antigen-presenting cells or cytokine responses. A new generation of spontaneous experimental autoimmune encephalomyelitis mouse models has been developed that mimic certain aspects of multiple sclerosis spectrum disorders. We assessed the effects of GA in the opticospinal encephalomyelitis model, which involves MOG35-55 peptide-specific T cells and B cells. A nonsignificant trend toward lower disease incidence was found for GA treatment (started on postnatal day 20). Immunohistochemical evaluations revealed no significant differences for inflammatory lesions and demyelination, cytokine production, proliferation, and cell surface markers of immune cells between GA-treated and PBS-treated (control) mice. Although a good correlation was found between the disease score of individual mice and some readout parameters (eg, immunohistochemical staining), this was not the case for others (eg, IFN-γ production). It seems plausible that a major effect of GA lies on alternative immunological pathways, such as initiating of an immune response that is not sufficiently reflected in this spontaneous experimental autoimmune encephalomyelitis model. Thus, the main advantage of the opticospinal encephalomyelitis model in our hands lies in the elucidation of factors influencing the onset of experimental autoimmune encephalomyelitis (eg, susceptibility factors). The model seems less suitable for investigation of disease severity modifications after therapeutic interventions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • Disease Models, Animal*
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Glatiramer Acetate
  • Mice, Transgenic
  • Peptides / pharmacology*
  • T-Lymphocytes / immunology


  • Peptides
  • Glatiramer Acetate