Literature DB >> 25002907

Defining a role for laquinimod in multiple sclerosis.

Bernd C Kieseier1.   

Abstract

Multiple sclerosis (MS), an inflammatory disease affecting the central nervous system, is considered to exhibit an important neurodegenerative component as well. Laquinimod is an orally administered quinoline-3-carboxamide under development for the treatment of MS. In vitro and animal studies have revealed various mechanisms by which laquinimod may exert its effects on the immune and nervous systems. These include effects on the innate immune system that promote the differentiation of anti-inflammatory/regulatory T cells, the activation of microglia cells, an increase in the expression of brain-derived neurotrophic factor, as well as the prevention of inflammation-induced excitotoxicity. Two phase III studies revealed the clinical benefits of laquinimod in patients with relapsing-remitting MS and exhibited a benign safety profile for this drug. Ongoing clinical trials will help to define the optimal dose and indication for laquinimod in MS. This article reviews current experimental and clinical evidence on the role of laquinimod in patients with this disabling disease.

Entities:  

Keywords:  laquinimod; multiple sclerosis; neuroprotection; relapsing–remitting multiple sclerosis

Year:  2014        PMID: 25002907      PMCID: PMC4082303          DOI: 10.1177/1756285614529615

Source DB:  PubMed          Journal:  Ther Adv Neurol Disord        ISSN: 1756-2856            Impact factor:   6.570


  24 in total

Review 1.  MRI evidence for multiple sclerosis as a diffuse disease of the central nervous system.

Authors:  Massimo Filippi; Maria Assunta Rocca
Journal:  J Neurol       Date:  2005-11       Impact factor: 4.849

2.  Laquinimod interferes with migratory capacity of T cells and reduces IL-17 levels, inflammatory demyelination and acute axonal damage in mice with experimental autoimmune encephalomyelitis.

Authors:  Christiane Wegner; Christine Stadelmann; Ramona Pförtner; Emanuel Raymond; Sara Feigelson; Ronen Alon; Bracha Timan; Liat Hayardeny; Wolfgang Brück
Journal:  J Neuroimmunol       Date:  2010-08-03       Impact factor: 3.478

3.  Modulation of autoimmune demyelination by laquinimod via induction of brain-derived neurotrophic factor.

Authors:  Jan Thöne; Gisa Ellrichmann; Silvia Seubert; Isabella Peruga; De-Hyung Lee; Rebecca Conrad; Liat Hayardeny; Giancarlo Comi; Stefan Wiese; Ralf A Linker; Ralf Gold
Journal:  Am J Pathol       Date:  2011-12-05       Impact factor: 4.307

4.  Insight into the mechanism of laquinimod action.

Authors:  W Brück; C Wegner
Journal:  J Neurol Sci       Date:  2011-03-22       Impact factor: 3.181

5.  Treatment with laquinimod reduces development of active MRI lesions in relapsing MS.

Authors:  C Polman; F Barkhof; M Sandberg-Wollheim; A Linde; O Nordle; T Nederman
Journal:  Neurology       Date:  2005-03-22       Impact factor: 9.910

6.  The new orally active immunoregulator laquinimod (ABR-215062) effectively inhibits development and relapses of experimental autoimmune encephalomyelitis.

Authors:  Charlott Brunmark; Anna Runström; Lennart Ohlsson; Birgitta Sparre; Thomas Brodin; Mikael Aström; Gunnar Hedlund
Journal:  J Neuroimmunol       Date:  2002-09       Impact factor: 3.478

Review 7.  Teriflunomide for the treatment of multiple sclerosis.

Authors:  Jiwon Oh; Paul W O'Connor
Journal:  Semin Neurol       Date:  2013-05-25       Impact factor: 3.420

8.  Effect of laquinimod on MRI-monitored disease activity in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study.

Authors:  G Comi; A Pulizzi; M Rovaris; O Abramsky; T Arbizu; A Boiko; R Gold; E Havrdova; S Komoly; Kw Selmaj; B Sharrack; M Filippi
Journal:  Lancet       Date:  2008-06-21       Impact factor: 79.321

9.  Reduced astrocytic NF-κB activation by laquinimod protects from cuprizone-induced demyelination.

Authors:  Wolfgang Brück; Ramona Pförtner; Trinh Pham; Jingya Zhang; Liat Hayardeny; Victor Piryatinsky; Uwe-Karsten Hanisch; Tommy Regen; Denise van Rossum; Lars Brakelmann; Karin Hagemeier; Tanja Kuhlmann; Christine Stadelmann; Gareth R John; Nadine Kramann; Christiane Wegner
Journal:  Acta Neuropathol       Date:  2012-07-06       Impact factor: 17.088

10.  Laquinimod, a quinoline-3-carboxamide, induces type II myeloid cells that modulate central nervous system autoimmunity.

Authors:  Ulf Schulze-Topphoff; Aparna Shetty; Michel Varrin-Doyer; Nicolas Molnarfi; Sharon A Sagan; Raymond A Sobel; Patricia A Nelson; Scott S Zamvil
Journal:  PLoS One       Date:  2012-03-30       Impact factor: 3.240

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  6 in total

1.  Laquinimod has no effects on brain volume or cellular CNS composition in the F1 3xTg-AD/C3H mouse model of Alzheimer's disease.

Authors:  Rehana Z Hussain; William A Miller-Little; Doris Lambracht-Washington; Tom C Jaramillo; Masaya Takahashi; Shanrong Zhang; Min Fu; Gary R Cutter; Liat Hayardeny; Craig M Powell; Roger N Rosenberg; Olaf Stüve
Journal:  J Neuroimmunol       Date:  2017-05-26       Impact factor: 3.478

Review 2.  The Use of Oral Disease-Modifying Therapies in Multiple Sclerosis.

Authors:  Benedikt Kretzschmar; Hannah Pellkofer; Martin S Weber
Journal:  Curr Neurol Neurosci Rep       Date:  2016-04       Impact factor: 5.081

3.  Flow cytometric analysis reveals the high levels of platelet activation parameters in circulation of multiple sclerosis patients.

Authors:  Agnieszka Morel; Joanna Rywaniak; Michał Bijak; Elżbieta Miller; Marta Niwald; Joanna Saluk
Journal:  Mol Cell Biochem       Date:  2017-02-16       Impact factor: 3.396

Review 4.  Manipulating Macrophage/Microglia Polarization to Treat Glioblastoma or Multiple Sclerosis.

Authors:  Thomas Kuntzel; Dominique Bagnard
Journal:  Pharmaceutics       Date:  2022-02-01       Impact factor: 6.321

Review 5.  NF-κB Pathways in the Pathogenesis of Multiple Sclerosis and the Therapeutic Implications.

Authors:  Saskia M Leibowitz; Jun Yan
Journal:  Front Mol Neurosci       Date:  2016-09-15       Impact factor: 5.639

Review 6.  Molecular Effects of FDA-Approved Multiple Sclerosis Drugs on Glial Cells and Neurons of the Central Nervous System.

Authors:  Kim M A De Kleijn; Gerard J M Martens
Journal:  Int J Mol Sci       Date:  2020-06-13       Impact factor: 5.923

  6 in total

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