Multiple sclerosis - established and novel therapeutic approaches.
Multiple sclerosis (MS) is the most common disabling neurological disease in young adults characterized by recurrent relapses and / or progression that are attributable to multifocal inflammation, demyelination and axonal pathology within the central nervous system. Currently approved disease-modifying treatments achieve their effects primarily by blocking the proinflammatory response in a nonspecific manner. Their limited clinical efficacy urges a more differentiated and specific therapeutic approach. Advances in understanding the pathophysiology of MS and appreciation of the contribution of neurodegenerative processes to disease pathology have led to promising therapeutic approaches at different points along the MS disease pathway: (i) monoclonal antibody therapy has provided the opportunity to rationally direct the therapeutic intervention by specifically targeting mechanisms of the immune system such as CD52 (alemtuzumab), CD25 (daclizumab), VLA-4 (natalizumab) and CD20 (rituximab); (ii) novel oral immunomodulating agents have shown to prevent lymphocyte recirculation from lymphoid organs such as fingolimod (FTY720); (iii) blocking of intracellular signaling cascades or ion channels at the cell-surface can protect axons from degeneration and restore axonal function in experimental settings; (iv) neuroprotective agents and stem cell therapy are able to promote remyelination and axonal regeneration in vitro. Despite the tremendous efforts undertaken, a better understanding of the sequential evolution of the MS lesion and the development of clinical surrogate markers, which allow to define subsets of patients with different forms of underlying pathogenesis, is necessary. This will pave the way for an optimized treatment approach, which will likely need both to target inflammation and to focus on promotion of neuroprotection and repair.
Ehling
Rainer
R
Clinical Department of Neurology, Innsbruck Medical University, Austria.
Berger
Thomas
T
Reindl
Markus
M
D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000276:immunology / Q000627:therapeutic use; D000077561:Daclizumab; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007107:Immune System / Q000502:physiology; D007074:Immunoglobulin G / Q000627:therapeutic use; D007155:Immunologic Factors / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D000069442:Natalizumab; D018696:Neuroprotective Agents / Q000627:therapeutic use; D000069283:Rituximab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D016207:Cytokines; D007074:Immunoglobulin G; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D000069442:Natalizumab; D018696:Neuroprotective Agents; D000074323:Alemtuzumab; D000069283:Rituximab; D000077561:Daclizumab