Insight into the mechanism of laquinimod action

Abstract

Laquinimod is a small, novel, orally active, well-tolerated molecule that significantly reduced gadolinium-enhancing lesions in patients with multiple sclerosis (MS). Orally administered laquinimod was found to be present within the central nervous system (CNS) in both healthy mice and mice with experimental autoimmune encephalomyelitis (EAE). Laquinimod inhibits development of both acute and chronic EAE. Furthermore, laquinimod minimizes inflammation, demyelination and axonal damage in MOG-induced EAE in mice treated at disease induction and following clinical disease onset. In vitro, laquinimod down-regulates secretion of pro-inflammatory cytokines and enhances production of anti-inflammatory cytokines from peripheral blood mononuclear cells (PBMCs) derived from healthy subjects and untreated relapsing remitting (RR) MS patients. Additionally, patients treated with laquinimod demonstrate up-regulation of brain-derived neurotrophic factor (BDNF) in the serum. In conclusion, treatment with laquinimod is effective in reducing inflammation, demyelination and axonal damage.