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.

• Authors: R E Gonsette
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 223 Issue 1 Pg. 87-93 (Aug 15 2004) ISSN: 0022-510X [Print] Netherlands
• PMID: 15261567 (Publication Type: Journal Article, Review)
• Copyright: Copyright 2004 Elsevier B.V.

Chemical References

• Antibodies, Monoclonal
• Immunosuppressive Agents
• Potassium Channel Blockers

Topics

• Animals
• Antibodies, Monoclonal (pharmacology, therapeutic use)
• Calcium Signaling (drug effects, immunology)
• Disease Models, Animal
• Humans
• Immunosuppressive Agents (pharmacology, therapeutic use)
• Immunotherapy (methods, trends)
• Multiple Sclerosis (drug therapy, immunology, physiopathology)
• Potassium Channel Blockers (pharmacology, therapeutic use)
• T-Lymphocytes (drug effects, immunology)