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Current and future therapies targeting the immune system in multiple sclerosis.
Curr Pharm Biotechnol 2014; 15(3):276-96CP

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 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.

Authors+Show Affiliations

No affiliation info availableNo affiliation info availableDepartment of Neurology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Strasse 22, 81675 Munich, Germany. hemmer@lrz.tu-muenchen.de.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

24938888

Citation

Loleit, Verena, et al. "Current and Future Therapies Targeting the Immune System in Multiple Sclerosis." Current Pharmaceutical Biotechnology, vol. 15, no. 3, 2014, pp. 276-96.
Loleit V, Biberacher V, Hemmer B. Current and future therapies targeting the immune system in multiple sclerosis. Curr Pharm Biotechnol. 2014;15(3):276-96.
Loleit, V., Biberacher, V., & Hemmer, B. (2014). Current and future therapies targeting the immune system in multiple sclerosis. Current Pharmaceutical Biotechnology, 15(3), pp. 276-96.
Loleit V, Biberacher V, Hemmer B. Current and Future Therapies Targeting the Immune System in Multiple Sclerosis. Curr Pharm Biotechnol. 2014;15(3):276-96. PubMed PMID: 24938888.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Current and future therapies targeting the immune system in multiple sclerosis. AU - Loleit,Verena, AU - Biberacher,Viola, AU - Hemmer,Bernhard, PY - 2013/11/18/received PY - 2014/05/31/revised PY - 2014/06/16/accepted PY - 2014/6/19/entrez PY - 2014/6/19/pubmed PY - 2015/6/17/medline SP - 276 EP - 96 JF - Current pharmaceutical biotechnology JO - Curr Pharm Biotechnol VL - 15 IS - 3 N2 - 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. SN - 1873-4316 UR - https://www.unboundmedicine.com/medline/citation/24938888/Current_and_future_therapies_targeting_the_immune_system_in_multiple_sclerosis_ L2 - http://www.eurekaselect.com/122791/article DB - PRIME DP - Unbound Medicine ER -