Limited effects of glatiramer acetate in the high-copy number hSOD1-G93A mouse model of ALS.
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.
Habisch
Hans-Jörg
HJ
Department of Neurology, University of Ulm, D89081 Ulm, Germany.
Schwalenstöcker
Birgit
B
Danzeisen
Ruth
R
Neuhaus
Oliver
O
Hartung
Hans-Peter
HP
Ludolph
Albert
A
D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D000818:Animals; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D000068717:Glatiramer Acetate; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009187:Myelitis / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D010243:Paralysis / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D015996:Survival Rate; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome
D016207:Cytokines; D007166:Immunosuppressive Agents; D010455:Peptides; C000606290:SOD1 protein, human; D000068717:Glatiramer Acetate; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1