Profile of oral laquinimod and its potential in the treatment of multiple sclerosis

Abstract

Abstract:The medications available to treat relapsing-remitting multiple sclerosis (RRMS) are expanding as newer, and more potent, disease-modifying treatments become available. In particular, there is an impetus for safe and effective oral options. Laquinimod is a novel oral immunomodulator currently under investigation for the treatment of RRMS. Although the exact mechanism of action is not known, laquinimod is not an immunosuppressant. Rather, it appears to have multiple effects on the immune system, including a shift to an anti-inflammatory cytokine state, reduction in antigen presentation, and effect on migration of T cells. In addition, laquinimod may have a neuroprotective effect. Phase II trials of RRMS patients showed a statistically significant reduction in magnetic resonance imaging (MRI) outcomes, such as decrease in gadolinium-enhancing lesions, and initial Phase III data have now shown a reduction in relapse rate, reduction in sustained disability, and a decrease in atrophy on brain MRI. In all trials, laquinimod has shown a favorable tolerability and safety profile. Laquinimod has been granted fast-track status by the US Food and Drug Administration, and may become an approved treatment for RRMS.

<p>Laquinimod Protects Against TNF-α-Induced Attachment of Monocytes to Human Aortic Endothelial Cells (HAECs) by Increasing the Expression of KLF2</p>

“…An early study on laquinimod found that it could disrupt the ability of very late antigen-4 to bind with VCAM-1, thereby potentially mitigating the migratory capacity of T cells. 31 A more recent study found that laquinimod could reduce the adhesiveness of the central nervous system endothelium through reduced expression of cellular adhesion molecules. 32 Here, we found that laquinimod could indeed reduce the expression of VCAM-1 and E-selectin induced by TNF-α.…”