The mechanism of action of glatiramer acetate in multiple sclerosis and beyond.
In multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE), the immune system reacts again self myelin constitutes in the central nervous system (CNS), initiating a detrimental inflammatory cascade that leads to demyelination as well as axonal and neuronal pathology. The amino acid copolymer glatiramer acetate (GA, Copaxone) is an approved first-line treatment for MS that has a unique mode of action. Accumulated evidence from EAE-induced animals and from MS patients indicates that GA affects various levels of the innate and the adaptive immune response, generating deviation from the pro-inflammatory to the anti-inflammatory pathway. This review aims to provide a comprehensive perspective on the diverse mechanism of action of GA in EAE/MS, in particular on the in situ immunomodulatory effect of GA and its ability to generate neuroprotective repair consequences in the CNS. In view of its immunomodulatory activity, the beneficial effect of GA in various models of other autoimmune related pathologies, such as immune rejection and inflammatory bowel disease (IBD) is noteworthy.
Department of Immunology, The Weizmann Institute of Science, Rehovot, 76100, Israel. rina.aharoni@weizmann.ac.il
Rina
R
Aharoni
D000818:Animals; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D000068717:Glatiramer Acetate; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000009:adverse effects / Q000502:physiology*; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D010455:Peptides / Q000009:adverse effects* / Q000627:therapeutic use*
D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D010455:Peptides; D000068717:Glatiramer Acetate