Treating multiple sclerosis with monoclonal antibodies

Abstract

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.

Keywords::

• adverse effects
• alemtuzumab
• autoimmune
• clinical trials
• daclizumab
• mechanism of action
• multiple sclerosis
• natalizumab
• neutralizing antibodies
• pharmacology
• progressive multifocal leukoencephalopathy
• rituximab
• Tysabri

Financial & competing interests disclosure

Mathias Buttmann and Peter Rieckmann have received honoraria from Bayer Schering Pharma AG, Merck Serono, Biogen Idec and Teva/Aventis for giving lectures. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.