title: In vitro assessment of the direct effect of laquinimod on basic functions of human neural stem cells and oligodendrocyte progenitor cells.
abstract: Laquinimod is an orally active immunomodulatory small molecule that has shown clear clinical benefit in trials for relapsing-remitting multiple sclerosis and in experimental rodent models that emulate multiple sclerosis (MS). Studies in healthy mice, and in mice with experimental autoimmune encephalomyelitis, have demonstrated that laquinimod is capable of entering the central nervous system. It is therefore important to determine if laquinimod is capable of a direct influence on basic functions of neural stem cells (NSC) or oligodendrocyte progenitor cells (OPC)--cells critical for myelin repair in MS. In order to address this question, a series of experiments was conducted to determine the effect of exogenous laquinimod on viability, proliferation, migration and differentiation of human NSC and OPC in vitro. These data show, for the first time in cells of human origin, that direct, short-term interaction between laquinimod and NSC or OPC, in an isolated in vitro setting, is not detrimental to the basic cellular function of these cells.
authors.affiliation: Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: kelland@usc.edu.
authors.forename: Eve E
authors.initials: EE
authors.lastname: Kelland
authors.affiliation: Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Gilmore
authors.affiliation: Pharmacology Unit, Global Innovative R&D, Teva Pharmaceutical Industries, Netanya, Israel.
authors.forename: Liat
authors.initials: L
authors.lastname: Hayardeny
authors.affiliation: Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Leslie P
authors.initials: LP
authors.lastname: Weiner
authors.affiliation: Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Brett T
authors.initials: BT
authors.lastname: Lund
mesh_terms: D001921:Brain / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects*; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D053595:Embryonic Stem Cells / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D009836:Oligodendroglia / Q000187:drug effects*; D015363:Quinolones / Q000494:pharmacology*; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D015363:Quinolones; C476223:laquinimod
keywords: Laquinimod; Multiple sclerosis; Neural stem cell; Oligodendrocyte progenitor cell