Abstract
A new orally active drug, laquinimod (ABR-215062), was shown to completely inhibit the development of murine acute experimental autoimmune encephalomyelitis (EAE). Furthermore, leukocyte infiltration into the central nervous system (CNS) was abolished in the laquinimod-treated animals. By direct comparison based on dose and total exposure, laquinimod was approximately 20 times more potent than the immunomodulator roquinimex. Laquinimod also had clear therapeutic effect when given after clinical onset in a chronic relapsing EAE model. It therefore represents a new orally active immunoregulatory drug without general immunosuppressive properties for the treatment of the autoimmune disease multiple sclerosis.
MeSH terms
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Adjuvants, Immunologic / pharmacology
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Animals
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Anti-Inflammatory Agents / pharmacology
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B-Lymphocytes / cytology
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B-Lymphocytes / drug effects
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B-Lymphocytes / immunology
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Cells, Cultured
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Central Nervous System / drug effects*
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Central Nervous System / immunology
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Central Nervous System / physiopathology
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Chemotaxis, Leukocyte / drug effects
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Chemotaxis, Leukocyte / immunology
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Dexamethasone / pharmacology
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Dose-Response Relationship, Drug
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Encephalomyelitis, Autoimmune, Experimental / drug therapy*
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Encephalomyelitis, Autoimmune, Experimental / prevention & control*
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Female
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Hydroxyquinolines / pharmacology*
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Immunosuppression Therapy
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Mice
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Mice, Inbred C57BL
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Multiple Sclerosis / drug therapy*
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Multiple Sclerosis / immunology
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Multiple Sclerosis / physiopathology
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Neuroimmunomodulation / drug effects*
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Neuroimmunomodulation / immunology
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Quinolones
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T-Lymphocytes / cytology
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology
Substances
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Adjuvants, Immunologic
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Anti-Inflammatory Agents
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Hydroxyquinolines
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Quinolones
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roquinimex
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Dexamethasone
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laquinimod