New immunosuppressants with potential implication in multiple sclerosis.

Abstract

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.