Recent insights into the mechanism of action of glatiramer acetate

Neurological Diseases in Relation to the Blood–Brain Barrier

“…However, the effects are transient and repeated treatments with high-dose steroids have too many complications to be used routinely. A more sustained reduction of BBB damage occurs with immunomodulatory drugs, such as interferon-b and glatiramer acetate (Filippi et al, 2011;Kala et al, 2011).…”

Glatiramoids

“…Numerous studies published in the scientific literature over recent decades have demonstrated that GA modulates innate and adaptive immune cell responses to promote anti-inflammatory and neuroprotective activities in various animal models of chronic inflammatory and neurodegenerative diseases (Aharoni et al 2000(Aharoni et al , 2003(Aharoni et al , 2005a(Aharoni et al , b, c, 2008(Aharoni et al , 2010Azoulay et al 2005;Dhib-Jalbut 2003;Gilgun-Sherki et al 2003;Hafler 2002;Hong et al 2005;Johnson 2010;Jung et al 2004;Kala et al 2010Kala et al , 2011Kipnis et al 2000Kipnis et al , 2003Kipnis and Schwartz 2002;Putheti et al 2003;Sand et al 2009;Schori et al 2001;Schwartz 2003;Stern et al 2008;Teitelbaum et al 1971Teitelbaum et al , 1988. The exact mechanisms of GA action in humans remains uncertain.…”

“…A study revealed that GA also induces HLA class I-restricted T-cell responses, suggesting that GA may also bind to HLA class Ia or class Ib molecules. These additional mechanisms may require cross-presentation or nonclassical HLA molecules (e.g., HLA-E) (Tennakoon et al 2006).The "promiscuous binding" capacity of GA peptides has been shown to successfully prevent or suppress EAE induced by different encephalitogenic antigens in a wide variety of animal species with different genetic backgrounds (Aharoni et al 2011;FridkisHareli and Strominger 1998;Kala et al 2011;Sela and Teitelbaum 2001).…”

“…Studies in EAE and MS patients have shown that GA can modulate cytokine secretion in specific subsets of B cells, increasing expression of anti-inflammatory cytokines, such as IL-10, IL-4, and TGF-β, which may in turn diminish production of proinflammatory cytokines, reduce autoreactive T-cell proliferation, and promote the generation of regulatory T cells (Kala et al 2010(Kala et al , 2011Matsushita et al 2008;Yanaba et al 2008). Studies in a murine model of EAE have also shown that B cells from GAtreated mice reduced expression of CD80 and CD86, costimulatory molecules on B cells that promote T cell activation (Kala et al 2010(Kala et al , 2011. In addition, purified B cells adoptively transferred from GA-treated mice suppressed EAE in recipient mice and inhibited the proliferation of autoreactive T cells and the development of Th1 and Th17 cells (Kala et al 2010).…”

Immunomodulatory medicines for multiple sclerosis: Progress and prospects

“…Copaxone is a random polymer of four amino acids (L-glutamic acid, L-lysine, L-alanine, and L-tyrosine) found in myelin basic protein. Its mechanism of action is unknown, but it may work as a decoy for the immune system [Schrempf and Ziemssen, 2007;Kala et al, 2011]. A recent systematic review of clinical trial data for Copaxone in MS indicates that the drug has partial efficacy in the treatment of RR-MS in terms of relapserelated clinical outcomes, but without any significant effect on clinical progression of disease, measured as sustained disability.…”