Inhibition of the development of chronic experimental autoimmune encephalomyelitis by laquinimod (ABR-215062) in IFN-β k.o. and wild type mice

Runström, Anna; Leanderson, Tomas; Ohlsson, Lennart; Axelsson, Bengt

doi:10.1016/j.jneuroim.2005.11.023

Cited by 63 publications

(43 citation statements)

References 20 publications

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“…Although the exact mechanism of action of laquinimod is unknown, in animal models, the drug reduces leukocyte infiltration into target tissues (glomeruli in SLE and optic nerves in multiple sclerosis), downregulates MHC class II gene expression (and hence antigen presentation), and modulates cytokine balance. [62][63][64] …”

Section: Newer Agents For Lupus Nephritis Will Be Tested In Combinatimentioning

confidence: 99%

Updates on the Treatment of Lupus Nephritis

Bomback

Appel

2010

Journal of the American Society of Nephrology

157

139

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Section: Newer Agents For Lupus Nephritis Will Be Tested In Combinatimentioning

confidence: 99%

Updates on the Treatment of Lupus Nephritis

Bomback

Appel

2010

Journal of the American Society of Nephrology

157

139

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“…These compounds have shown efficacy in several mouse models of inflammatory autoimmune disease [29][30][31][32][33] and they are currently in clinical development for multiple sclerosis [34][35][36][37], systemic sclerosis and prostate cancer [38,39]. Recently, the S100A9 protein was identified as one molecular target of the Q-compound paquinimod (ABR-215757) [40].…”

Section: Introductionmentioning

confidence: 99%

The quinoline-3-carboxamide paquinimod (ABR-215757) reduces leukocyte recruitment during sterile inflammation: Leukocyte- and context-specific effects

Deronic

Helmersson

Leanderson

et al. 2014

International Immunopharmacology

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“…Sub-optimal responders to Copaxonemay greatly benefit from safe synergistic combination therapies such as Laquinimod. Currently in clinical trials for MS, Laquinimod has been reported to result in similar effects of GA including altering dendritic cells, inducing type II monocytes, increasing T and B regulatory cells, decreasing antigen presentation, and direct neuroprotective effects [104][105][106][107][108][109][110][111][112][113][114][115][116][117]. The novelty of this study is that a direct functional effect of GA on B lymphocytes has not been previously reported.…”

Section: Discussionmentioning

confidence: 98%

B Cell Receptor Recognition of Glatiramer Acetate is Required for Efficacy through Antigen Presentation and Cytokine Production

Jackson

Selva²,

Niedzielko³

et al. 2014

J Clin Cell Immunol

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Multiple Sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS) leading to neuronal demyelination, lack of remyelination, and axonal loss. If left untreated, patients inevitably suffer from severe cognitive, psychological and physical disabilities.Although not yet approved, B cell depletion achieved with anti-CD20 monoclonal antibodies is the most effective therapy to-date in MS patients. As this therapeutic depletes immune cells potentially important in pathogen immunity, an immense need remains for highly efficacious therapeutics maintaining a favorable safety profile. Even amongst the emergence of new therapeutic options for patients with MS, the myelin basic protein mimetic, Copaxone (glatiramer acetate, GA), remains the most commonly prescribed drug in the United States. As specific B cell depletion appears to be the most effective therapy for MS patients, the goal of this study was to further elucidate the mechanism of action of GA on B lymphocytes. Our studies show that GA directly interacts with human and murine B cell receptors (BCR) inducing the activation of B lymphocytes and BCR recognition of GA is required for efficacy in an animal model of MS. GA loaded B lymphocytes resulted in IL-2 production from CD4 + T cells suggesting B lymphocytes serve as an antigen presentation source for GA. In fifty-percent of the MS patients tested, GA stimulation reduced baseline levels of the pro-inflammatory cytokines IL-6 and TNFα in purified B lymphocytes, while other cytokines were not consistently altered. Taken together, this data suggests that the mechanism of action of GA on B lymphocytes includes the presentation of GA to T lymphocytes in the context of an anti-inflammatory cytokine milieu. The results from this study provide a strong foundation for future exploration of optimal Copaxone responders or synergistic combination therapies with an improved risk: benefit ratio compared to currently approved therapeutics for MS.

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Inhibition of the development of chronic experimental autoimmune encephalomyelitis by laquinimod (ABR-215062) in IFN-β k.o. and wild type mice

Cited by 63 publications

References 20 publications

Updates on the Treatment of Lupus Nephritis

Updates on the Treatment of Lupus Nephritis

The quinoline-3-carboxamide paquinimod (ABR-215757) reduces leukocyte recruitment during sterile inflammation: Leukocyte- and context-specific effects

B Cell Receptor Recognition of Glatiramer Acetate is Required for Efficacy through Antigen Presentation and Cytokine Production

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