Novel Immunosuppressive Therapy by M2000 in Experimental Multiple Sclerosis

• Published in: Immunopharmacology and immunotoxicology 2005, Vol.27 (2), p.255-265
• Main Authors: Mirshafiey, Abbas, Matsuo, Hidenori, Nakane, Shunya, Rehm, Bernd H.A., Koh, Chang-Sung, Miyoshi, Seiji
• Format: Article
• Language: English
• Subjects: Animals; Anti-inflammatory; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Cell Line, Tumor - drug effects; Cell Proliferation; Dose-Response Relationship, Immunologic; EAE; Encephalomyelitis, Autoimmune, Experimental - chemically induced; Encephalomyelitis, Autoimmune, Experimental - drug therapy; Encephalomyelitis, Autoimmune, Experimental - immunology; Female; Hexuronic Acids - administration & dosage; Hexuronic Acids - pharmacology; Immunization; Immunosuppressive; Immunosuppressive Agents - pharmacology; Lymph Nodes - cytology; Lymph Nodes - drug effects; M2000; Multiple sclerosis; Multiple Sclerosis - drug therapy; Mycobacterium tuberculosis; Myelin Basic Protein; NSAIDs; Rats; Rats, Inbred Lew; Time Factors
• ISSN: 0892-3973; 1532-2513
• DOI: 10.1081/IPH-200067751

The therapeutic potency of M2000 (β-D-mannuronic acid), a novel designed nonsteroidal anti-inflammatory drug with immunosuppressive property in T-cell-mediated autoimmune disease, was tested. The influence of M2000 on myelin basic protein (MBP)-induced experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, was assessed. M2000 at two doses, 40 and 80 mg/kg/day, was administered intraperitoneally (i.p.) to prevention and treatment groups, respectively. Onset of i.p. injections of M2000 to prophylactic and therapeutic groups was day-1 and day-7 postimmunization. The WEHI-164 cell line was used for assaying the tolerability against M2000. The results of this experiment showed that the treatment of EAE with M2000 could significantly suppress disease development both prophylactically and therapeutically; the onset and symptoms of EAE in Lewis rats could be suppressed following the administration of M2000. Clinical improvement was accompanied by a marked decrease in mean numbers of vessels with perivascular cellular infiltration in M2000-treated rats compared with nontreated control. Disease suppression was associated with a marked suppression of MBP-specific T-cell reactivity in vitro, without any evidence for a generalized impairment of T-cell activity. Moreover, M2000 also showed a very high tolerability compared with certain steroidal and nonsteroidal anti-inflammatory drugs. Collectively, our data suggest that M2000 may provide a novel therapeutic option for T-cell-mediated autoimmune diseases in animal models and possibly in humans.