title: Laquinimod, an up-and-coming immunomodulatory agent for treatment of multiple sclerosis.
abstract: Laquinimod is a novel oral drug that is currently being evaluated for the treatment of relapsing-remitting multiple sclerosis (RRMS). Although the mode of action of laquinimod remains to be fully elucidated, current knowledge indicates that laquinimod exerts beneficial activities both on the peripheral immune system and within the central nervous system (CNS). The immunomodulatory properties have been deciphered primarily from studies of laquinimod in the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Data indicate that laquinimod has a primary effect on innate immunity. Laquinimod modulates the function of various myeloid antigen presenting cell populations, which then downregulate proinflammatory T cell responses. Further, data also indicate that laquinimod acts directly on resident cells within the CNS to reduce demyelination and axonal damage. Results from clinical trials that tested laquinimod in RRMS demonstrated that it reduced relapse rate and the mean cumulative number of active lesions, and had a more marked reduction in disability progression than relapse rate. Laquinimod treatment was associated with an excellent safety and tolerability profile. These data indicate that laquinimod will offer a valuable new treatment option for RRMS patients.
authors.affiliation: Department of Neurology, University of California, San Francisco, CA 94158, USA.
authors.forename: Michel
authors.initials: M
authors.lastname: Varrin-Doyer
authors.affiliation: Department of Neurology, University of California, San Francisco, CA 94158, USA. Electronic address: zamvil@ucsf.neuroimmunol.org.
authors.forename: Scott S
authors.initials: SS
authors.lastname: Zamvil
authors.affiliation: Department of Neurology, University of California, San Francisco, CA 94158, USA.
authors.forename: Ulf
authors.initials: U
authors.lastname: Schulze-Topphoff
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology*; D015363:Quinolones / Q000627:therapeutic use*
chemical_list: D007155:Immunologic Factors; D015363:Quinolones; C476223:laquinimod
keywords: Disease modifying therapy; Experimental autoimmune encephalomyelitis; Immunomodulation; Laquinimod; Multiple sclerosis
references.citation: Cell. 1995 Mar 10;80(5):707-18
references.pmid: 7534215
references.citation: J Med Chem. 2004 Apr 8;47(8):2075-88
references.pmid: 15056005
references.citation: J Neurol Neurosurg Psychiatry. 2014 Aug;85(8):851-8
references.pmid: 24029546
references.citation: J Exp Med. 2013 Dec 16;210(13):2921-37
references.pmid: 24323356
references.citation: J Neuroimmunol. 2010 Apr 15;221(1-2):87-94
references.pmid: 20347159
references.citation: Am J Pathol. 2012 Jan;180(1):267-74
references.pmid: 22152994
references.citation: J Neuroimmunol. 2012 Oct 15;251(1-2):45-54
references.pmid: 22846497
references.citation: Expert Rev Clin Pharmacol. 2012 May;5(3):245-56
references.pmid: 22697588
references.citation: J Neuroimmunol. 2002 Sep;130(1-2):163-72
references.pmid: 12225898
references.citation: Neurotherapeutics. 2007 Oct;4(4):647-53
references.pmid: 17920545
references.citation: J Neuroimmunol. 2013 Oct 15;263(1-2):108-15
references.pmid: 23920036
references.citation: Annu Rev Immunol. 2002;20:101-23
references.pmid: 11861599
references.citation: Acta Neuropathol. 2012 Sep;124(3):411-24
references.pmid: 22766690
references.citation: Mult Scler. 2010 Nov;16(11):1360-6
references.pmid: 20834039
references.citation: Neuropharmacology. 2002 Apr;42(5):731-9
references.pmid: 11985832
references.citation: Science. 2007 Jan 5;315(5808):107-11
references.pmid: 17204652
references.citation: Neurology. 2000 May 9;54(9):1726-33
references.pmid: 10802775
references.citation: Brain. 2007 Apr;130(Pt 4):1089-104
references.pmid: 17438020
references.citation: Brain. 2010 Aug;133(Pt 8):2248-63
references.pmid: 20826430
references.citation: J Neurol Sci. 2011 Jul 15;306(1-2):173-9
references.pmid: 21429524
references.citation: N Engl J Med. 2008 Feb 14;358(7):676-88
references.pmid: 18272891
references.citation: Neurology. 2000 May 9;54(9):1734-41
references.pmid: 10802777
references.citation: Brain. 2013 Apr;136(Pt 4):1048-66
references.pmid: 23518712
references.citation: J Neuroimmunol. 2012 Oct 15;251(1-2):14-24
references.pmid: 22749337
references.citation: J Neuroimmunol. 2004 Nov;156(1-2):3-9
references.pmid: 15465591
references.citation: Trends Immunol. 2005 Nov;26(11):565-71
references.pmid: 16153891
references.citation: Lancet. 2008 Jun 21;371(9630):2085-92
references.pmid: 18572078
references.citation: Trends Neurosci. 2005 Jan;28(1):5-11
references.pmid: 15626491
references.citation: J Am Soc Nephrol. 2010 Dec;21(12):2028-35
references.pmid: 21051743
references.citation: J Neuroimmunol. 2010 Oct 8;227(1-2):133-43
references.pmid: 20684995
references.citation: PLoS One. 2012;7(3):e33797
references.pmid: 22479444
references.citation: J Neurol. 2014 Apr;261(4):773-83
references.pmid: 24535134
references.citation: N Engl J Med. 2012 Mar 15;366(11):1000-9
references.pmid: 22417253
references.citation: Annu Rev Immunol. 1990;8:579-621
references.pmid: 2188675
references.citation: Neurology. 2005 Mar 22;64(6):987-91
references.pmid: 15781813