New immunosuppressants with potential implication in multiple sclerosis.
New immunosuppressants are consistently developed to treat autoimmune diseases and some of them might have implications in multiple sclerosis (MS). A new antiproliferative agent, pixantrone, an analogue of mitoxantrone (MX), has a much lower cardiotoxicity and exerts the same potent immunosuppressive effects in experimental allergic encephalomyelitis (EAE). A phase I trial in MS patients is planned in the next future. New monoclonal antibodies (mAb) and other biological constructs containing foreign proteins are developed but their potential immunogenicity is a considerable drawback to their long-term administration. In addition, their beneficial effects in MS are not evident so far. Small molecules targeting the voltage-gated Kv1.3K+ channel regulating CA2+ signaling in T lymphocytes, specifically target activated, pathogenic T cells. Already found effective in EAE, those agents would be easier to handle than T-cell vaccination. Two new immunosuppressants with a unique mechanism of action (FTY720 and Epomycine M) selectively impair autoreactive T-cell homing, without affecting the other components of the immune response. The potent protective effect of TRY720 has been demonstrated in EAE and a phase I trial in MS appears warranted. Finally, a new concept about immunosuppressive treatments in organ transplantation, "tolerogenic immunosuppression", may have potential in MS.
Gonsette
R E
RE
National Center for Multiple Sclerosis, Vanheylenstraat 16, Melsbroek B-1820, Belgium. r.gonsette@skynet.be
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D020013:Calcium Signaling / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods* / Q000639:trends*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D026902:Potassium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D026902:Potassium Channel Blockers