Current treatment strategies for multiple sclerosis - efficacy versus neurological adverse effects

Department of Neurology, Technische Universität München, Munich, Germany.
Current pharmaceutical design (Impact Factor: 3.29). 02/2012; 18(2):209-19. DOI: 10.2174/138161212799040501
Source: PubMed

ABSTRACT Recent years have broadened the spectrum of therapeutic strategies and specific agents for treatment of multiple sclerosis (MS). While immune-modulating drugs remain the first-line agents for MS predominantly due to their benign safety profile, our growing understanding of key processes in initiation and progression of MS has pioneered development of new agents with specific targets. One concept of these novel drugs is to hamper migration of immune cells towards the affected central nervous system (CNS). The first oral drug approved for MS therapy, fingolimod inhibits egress of lymphocytes from lymph nodes; the monoclonal antibody natalizumab prevents inflammatory CNS infiltration by blocking required adhesion molecules. The second concept is to deplete T cells and/or B cells from the peripheral circulation using highly specific monoclonal antibodies such as alemtuzumab (anti-CD52) or rituximab/ocrelizumab (anti-CD20). All of these novel, highly effective agents are a substantial improvement in our therapeutic armamentarium; however, they have in common to potentially lower the abundance of immune cells within the CNS, thereby collaterally affecting immune surveillance within this well-controlled compartment. In this review, we aim to critically evaluate the risk/benefit ratio of therapeutic strategies in treatment of MS with a specific focus on infectious neurological side effects.

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    • "The unique feature of anti-SEMA4D therapy is that it combines independent mechanisms of action that overlap with the anti-inflammatory effects of several of these clinical agents and further extends activity to restoring and protecting the integrity of both BBB and myelinated axons. While approved immunosuppressive and anti-inflammatory drugs have been shown to be effective in transiently suppressing MS-related symptoms and relapse frequency, many have significant side-effects with varying degrees of severity (Weber et al., 2012). In animal studies and ongoing phase 1 clinical trials to date, anti-SEMA4D antibody administration has not been associated with significant overt toxicity. "
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    Neurobiology of Disease 10/2014; 73. DOI:10.1016/j.nbd.2014.10.008 · 5.20 Impact Factor
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    • "Multiple sclerosis (MS) is a chronic neuroinflammatory disease characterized by infiltration of peripheral immune cells into the CNS through an impaired blood-brain barrier (BBB) or blood-spinal cord barrier (BSCB), and loss of myelin with accompanying scarring of axons (McFarland and Martin, 2007). However, most current treatments for MS only offer palliative relief without providing a cure, and many are also associated with adverse effects that limit their long-term utility (Weber et al., 2012). "
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