Treating multiple sclerosis with monoclonal antibodies.
Therapeutic monoclonal antibodies (mAbs) are potent new tools for a molecular targeted approach to modify the course of multiple sclerosis (MS). Besides natalizumab, which was approved in 2006, three other mAbs (alemtuzumab, rituximab and daclizumab) were successfully tested in Phase II MS trials. In this review, introductory notes on the development and systematic nomenclature of therapeutic mAbs in general, set the stage for a detailed discussion of the four mAbs mentioned. We summarize non-MS indications, expression and function of target antigens, scientific rationales for MS therapy, putative modes of action and pharmacological aspects. Particularly, we provide a critical discussion of clinical MS trials, including protocols and interim analyses of trials currently underway. The natalizumab section pays special attention to the clinical handling of safety issues and the diagnostic use of neutralizing antibodies. We finally develop a scenario for how each of the four mAbs might evolve into the market of MS therapeutics within the coming years.
Buttmann
Mathias
M
Julius-Maximilians University, Department of Neurology, Josef-Schneider-Str. 11, 97080 Würzburg, Germany. m.buttmann@uni-wuerzburg.de
Rieckmann
Peter
P
D000074323:Alemtuzumab; D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm / Q000009:adverse effects / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D000077561:Daclizumab; D017277:Drug Approval; D016503:Drug Delivery Systems; D019317:Evidence-Based Medicine; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology / Q000628:therapy*; D000069442:Natalizumab; D016032:Randomized Controlled Trials as Topic; D000069283:Rituximab; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; D007074:Immunoglobulin G; D000069442:Natalizumab; D000074323:Alemtuzumab; D000069283:Rituximab; D000077561:Daclizumab