Limited effects of glatiramer acetate in the high-copy number hSOD1-G93A mouse model of ALS

Exp Neurol. 2007 Aug;206(2):288-95. doi: 10.1016/j.expneurol.2007.05.007. Epub 2007 May 18.

Abstract

In amyotrophic lateral sclerosis (ALS), an involvement of the immune system in the degenerative processes has been shown in both humans and the transgenic SOD1-G93A mice. We previously showed that Glatiramer acetate (also known as copolymer-1; COP-1; Copaxone) improves motor function and extends survival times in an inbred strain of ALS mice probably by interacting with pro-inflammatory T(H) lymphocytes. In the course of this study we tested whether these beneficial effects could be reproduced by repeated vaccination of animals with COP-1 without co-administration of complete Freund's adjuvant. In an outbred strain we could not demonstrate a positive effect of COP-1 on survival times, but found a significant improvement of motor performance during the late stage of disease and a moderate decrease of the production of the inflammatory cytokines interferon-gamma and IL-4 by T lymphocytes isolated from the mice's spleen. In conclusion, the effects of COP-1 in the applied hybrid strain displaying a faster disease progression were less pronounced than in the earlier tested inbred strain of ALS mice.

MeSH terms

  • Amyotrophic Lateral Sclerosis / drug therapy*
  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / immunology
  • Animals
  • Cytokines / immunology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Gene Dosage / genetics
  • Glatiramer Acetate
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Mice
  • Mice, Transgenic
  • Myelitis / drug therapy*
  • Myelitis / genetics
  • Myelitis / immunology
  • Paralysis / drug therapy
  • Paralysis / immunology
  • Paralysis / prevention & control
  • Peptides / pharmacology*
  • Peptides / therapeutic use
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase-1
  • Survival Rate
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Treatment Outcome

Substances

  • Cytokines
  • Immunosuppressive Agents
  • Peptides
  • SOD1 protein, human
  • Glatiramer Acetate
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1