Current and Future Therapies Targeting the Immune System in Multiple Sclerosis
Verena Loleit, Viola Biberacher and Bernhard Hemmer
Affiliation: Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Strasse 22, 81675 Munich, Germany.
Keywords: Dimethyl fumarate, fingolimod, glatiramer acetate, interferons, multiple sclerosis, natalizumab, teriflunomide.
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 have been transferred from bench to bedside. The α4β-integrin-antagonist natalizumab was
approved in 2005. Fingolimod, dimethyl fumarate and teriflunomide were the first oral drugs introduced in MS therapy.
Recently alemtuzuab, another monoclonal antibody, was approved in Europe. 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.
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