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Current Pharmaceutical Biotechnology
ISSN (Print): 1389-2010
ISSN (Online): 1873-4316
Epub Full Text Article
DOI: 10.2174/1389201015666140617104332      Price:  $95









Current and Future Therapies Targeting the Immune System in Multiple Sclerosis

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Author(s): Verena Loleit, Viola Biberacher and Bernhard Hemmer
Abstract:
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). The exact pathomechanism is unknown, but an aberrant immune response against CNS antigens, leading to inflammation in brain and spinal cord followed by demyelination, axonal damage and scar formation, seems to play a major role. Later in the disease course, inflammation decreases, while neurodegeneration proceeds. Approximately 80% of the patients initially show a relapsing-remitting disease course (RRMS), but the majority of them later develops a secondary progressive MS (SPMS). A minority suffers from primary progressive MS (PPMS).

Primary goals of long-term MS therapy are to prevent relapses and disease progression. Assuming that MS is an autoimmune disease, most therapeutics aim to modulate or suppress the immune system. Until now many drugs have proven efficacy in RRMS, but none in PPMS. Interferon-β (IFN-β) and glatiramer acetate are known in RRMS therapy for years. Based on preclinical research and clinical trials, new treatment strategies have emerged and were transferred from bench to bedside. The 4β-integrin-antagonist natalizumab was approved in 2005. Fingolimod, BG12 and teriflunomide were the first oral drugs introduced in MS therapy. Recently alemtuzuab another monoclonal antibody was approved. Promising future perspectives are alemtuzumab, daclizumab, and laquinimod.

Here, we review drug mechanisms in the therapy of MS. The mechanisms of action and the effect of the drugs on the immune system are summarized. We report recent results of clinical trials, highlight special features of different treatment strategies, and discuss future perspectives and ongoing clinical trials

Affiliation:
Department of Neurology Klinikum rechts der Isar Technische Universität München Ismaninger Strasse 22 81675 Munich, Germany