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The role of laquinimod in modulation of the immune response in relapsing–remitting multiple sclerosis: Lessons from gene expression signatures
R. Zilkha-Falb, M. Gurevich, L. Hayardeny, A. Achiron
Journal of Neuroimmunology, Volume 283, 15 June 2015, Pages 11-16
- Laquinimod down-regulates leukocyte extravasation.
- Laquinimod down-regulates pro-inflammatory cytokines.
- The key TGFb signaling pathway is down-regulated by laquinimod.
Laquinimod, is a potential oral immunomodulatory drug, for relapsing–remitting multiple sclerosis (RRMS). We analyzed the blood-transcriptional changes in RRMS patients (who participated in the ALLEGRO clinical trial) at one and six months after laquinimod treatment using gene expression microarrays. The molecular effects of laquinimod were enhanced by duration of treatment and showed down-regulation of inflammatory responses mainly via TGFb signaling, and of pro-inflammatory cytokines as well as of cellular movement, including adhesion, migration and leukocyte extravasation signaling. Our results demonstrate that laquinimod suppresses inflammation through down-regulation of inflammatory cytokines and arrest of leukocyte extravasation and thereby could attenuate disease activity in RRMS patients.