Laquinimod

Laquinimod (ABR-215062) is an immunoregulator derived from Linomide, has been shown to completely inhibit the development of murine acute experimental autoimmune encephalomyelitis (EAE) ; dose-dependently reduces the incidence of EAN, ameliorated clinical signs and inhibited P0 peptide 180-199-specific T cell responses as well as also the decreased inflammation and demyelination in the peripheral nerves; shows improved potency and superior toxicological profile compared to the lead compound Roquinimex (Linomide) .Multiple Sclerosis Approved (In Vitro) :Laquinimod reverses EAE and inhibits pathogenic T cell immune responses. Laquinimod reverses RR-EAE and inhibits inflammatory T cell responses via a direct effect on myeloid APC. Laquinimod alters myeloid APC subsets and inhibits Th1 and Th17 polarization of myelin-specific T cells. Laquinimod-induced type II (M2) monocytes reverse established EAE. Laquinimod modulates the phenotype of B cells of healthy donors. Laquinimod modulates expression of markers related to regulatory capacity in B cells of RRMS patients. Laquinimod reduces IFNγ cytokine expression in CD4+ T cells. (In Vivo) :Laquinimod treatment inhibits donor myelin-specific T cells from transferring EAE to naive recipient mice. In vivo laquinimod treatment alters subpopulations of myeloid antigen presenting cells (APC) that include a decrease in CD11c+CD11b+CD4+ dendritic cells (DC) and an elevation of CD11bhiGr1hi monocytes.