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

被引：142

作者：

Brunmark, C ^{[1
]}

Runström, A ^{[1
]}

Ohlsson, L ^{[1
]}

Sparre, B ^{[1
]}

Brodin, T ^{[1
]}

Åström, M ^{[1
]}

Hedlund, G ^{[1
]}

机构：

[1] Act Biotech Res AB, S-22007 Lund, Sweden

来源：

JOURNAL OF NEUROIMMUNOLOGY | 2002年 / 130卷 / 1-2期

关键词：

EAE/MS; autoinimunity; immunomodulators; immunochemistry; in vivo animal models;

D O I：

10.1016/S0165-5728(02)00225-4

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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 immumoregulatory drug without general immunosuppressive properties for the treatment of the autoimmune disease multiple sclerosis. (C) 2002 Elsevier Science B.V. All rights reserved.

引用

收藏

页码：163 / 172

页数：10

相关论文

共 23 条

[1] Copolymer 1 induces T cells of the T helper type 2 that crossreact with myelin basic protein and suppress experimental autoimmune encephalomyelitis [J].

Aharoni, R ;

Teitelbaum, D ;

Sela, M ;

Arnon, R .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (20) :10821-10826

[2] Linomide reduces the rate of active lesions in relapsing-remitting multiple sclerosis [J].

Andersen, O ;

Lycke, J ;

Tollesson, PO ;

Svenningsson, A ;

Runmarker, B ;

Linde, AS ;

Astrom, M ;

Gjorstrup, P ;

Ekholm, S .

NEUROLOGY, 1996, 47 (04) :895-900

[3]

Arnason BGW, 1999, ANNU REV MED, V50, P291

[4] Linomide suppresses acute experimental autoimmune encephalomyelitis in Lewis rats by counter-acting the imbalance of pro-inflammatory versus anti-inflammatory cytokines [J].

Diab, A ;

Michael, L ;

Wahren, B ;

Deng, GM ;

Björk, J ;

Hedlund, G ;

Zhu, J .

JOURNAL OF NEUROIMMUNOLOGY, 1998, 85 (02) :146-154

[5] LINOMIDE INHIBITS PROGRAMMED CELL-DEATH OF PERIPHERAL T-CELLS IN-VIVO [J].

GONZALO, JA ;

GONZALEZGARCIA, A ;

KALLAND, T ;

HEDLUND, G ;

MARTINEZA, C ;

KROEMER, G .

EUROPEAN JOURNAL OF IMMUNOLOGY, 1994, 24 (01) :48-52

[6] CHANGES IN HYPOTHALAMIC CORTICOTROPIN-RELEASING FACTOR AND ANTERIOR-PITUITARY PROOPIOMELANOCORTIN MESSENGER-RNA DURING THE COURSE OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS [J].

HARBUZ, MS ;

LEONARD, JP ;

LIGHTMAN, SL ;

CUZNER, ML .

JOURNAL OF NEUROIMMUNOLOGY, 1993, 45 (1-2) :127-132

[7] Linomide enhances apoptosis in CD4(+)CD8(+) thymocytes [J].

Harring, AC ;

Xu, Z ;

Andersson, G ;

Hedlund, G .

SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 1997, 46 (05) :488-494

[8] Effects of Linomide on immune cells and cytokines inhibit autoimmune pathologies of the central and peripheral nervous system [J].

Hedlund, G ;

Link, H ;

Zhu, J ;

Xiao, BG .

INTERNATIONAL IMMUNOPHARMACOLOGY, 2001, 1 (06) :1123-1130

[9] CHRONIC EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS INDUCED BY THE 89-101 MYELIN BASIC-PROTEIN PEPTIDE IN B10RIII (H-2R) MICE [J].

JANSSON, L ;

OLSSON, T ;

HOJEBERG, B ;

HOLMDAHL, R .

EUROPEAN JOURNAL OF IMMUNOLOGY, 1991, 21 (03) :693-699

[10] INHIBITION OF ACUTE, EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS BY THE SYNTHETIC IMMUNOMODULATOR LINOMIDE [J].

KARUSIS, DM ;

LEHMANN, D ;

SLAVIN, S ;

VOURKAKARUSSIS, U ;

MIZRACHIKOLL, R ;

OVADIA, H ;

BENNUM, A ;

KALLAND, T ;

ABRAMSKY, O .

ANNALS OF NEUROLOGY, 1993, 34 (05) :654-660