[Development of new therapies for multiple sclerosis].
ABSTRACT Current first line treatment for multiple sclerosis is only moderately effective and is associated with frequent and disturbing side effects. We here describe opportunities and challenges related to drugs under development.
Non-systematic search in PubMed and congress abstracts.
Monoclonal antibodies (e.g. natalizumab, alemtuzumab, rituximnab and dacklizumab) and oral agents (e.g. fingolimod and cladribine) target molecules or cells which are important in the immunopathogenesis of multiple sclerosis. These agents seem to have a considerable effect on relapsing-remitting multiple sclerosis, but may also be associated with serious side effects. Natalizumab is licensed as second line treatment for relapsing-remitting multiple sclerosis, and also as first line treatment in especially serious cases. Cladribine and fingolimod may be available in Norway in 2011.
Treatment of exacerbations in multiple sclerosis is changing. Indication for the drugs under development is not yet clear.
- SourceAvailable from: Alexandre Bueno Merlini[Show abstract] [Hide abstract]
ABSTRACT: Rituximab, a mouse-human chimeric monoclonal antibody, exerts its effect by binding to the CD20 antigen, a transmembrane protein expressed on the surface of B cells, resulting in depletion of this B-lymphocyte lineage. It recognizes a discontinuous epitope composed by two sequences of 170-173 and 182-185 amino acids expressed on the CD20+ cells. This binding entails a fast depletion of normal and damaged B cells, resulting in decrease of their immunogenic properties. Besides the CD20+ B-cell depletion per se, other different immunologic mechanisms have been proposed, which include cellular and complement dependent cytotoxicity, induction of oncogen-myc and MHC class II expression, and direct apoptosis induction. The pre-apoptotic mechanism, verified in vitro, it is explained by the translocation of phosphatidylserine (a component of phospholipidic cell membrane), which is kept in the Rituximab: Pharmacology, Clinical Uses and Health Effects, 11/2012: chapter Rituximab: update on pharmacology and clinical applications: pages 31-46; Nova Publishers., ISBN: 978-1-62257-533-6