Multiple sclerosis therapies: molecular mechanisms and future.
The current treatments for multiple sclerosis (MS) are, by many measures, not satisfactory. The original interferon-β therapies were not necessarily based on an extensive knowledge of the pathophysiological mechanisms of the disease. As more and more insight has been acquired about the autoimmune mechanisms of MS and, in particular, the molecular targets involved, several treatment approaches have emerged. In this chapter, we highlight both promising preclinical approaches and therapies in late stage clinical trials that have been developed as a result of the improved understanding of the molecular pathophysiology of MS. These clinical stage therapies include oral agents, monoclonal antibodies, and antigen-specific therapies. Particular emphasis is given to the molecular targets when known and any safety concerns that have arisen because, despite the need for improved efficacy, MS remains a disease in which the safety of any agent remains of paramount importance.
Fontoura
Paulo
P
Roche Pharmaceuticals, CNS Translational Medicine Group, Basel, Switzerland.
Garren
Hideki
H
D000074323:Alemtuzumab; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D017338:Cladribine / Q000627:therapeutic use; D003437:Crotonates / Q000627:therapeutic use; D000077561:Daclizumab; D000069462:Dimethyl Fumarate; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000628:therapy; D000068876:Fingolimod Hydrochloride; D005650:Fumarates / Q000627:therapeutic use; D006801:Humans; D006885:Hydroxybutyrates; D007074:Immunoglobulin G / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods* / Q000639:trends; D051379:Mice; D009103:Multiple Sclerosis / Q000209:etiology / Q000276:immunology / Q000628:therapy*; D004676:Myelin Basic Protein / Q000627:therapeutic use; D009570:Nitriles; D010446:Peptide Fragments / Q000627:therapeutic use; D011409:Propylene Glycols / Q000627:therapeutic use; D015363:Quinolones / Q000627:therapeutic use; D000069283:Rituximab; D013110:Sphingosine / Q000031:analogs & derivatives / Q000627:therapeutic use; D014052:Toluidines / Q000627:therapeutic use; D019444:Vaccines, DNA / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; C544595:BHT 3009; D003437:Crotonates; D005650:Fumarates; D006885:Hydroxybutyrates; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D004676:Myelin Basic Protein; D009570:Nitriles; D010446:Peptide Fragments; D011409:Propylene Glycols; D015363:Quinolones; D014052:Toluidines; D019444:Vaccines, DNA; C527525:teriflunomide; C526227:MBP-8298; D000074323:Alemtuzumab; D017338:Cladribine; D000069283:Rituximab; C476223:laquinimod; D000077561:Daclizumab; D000069462:Dimethyl Fumarate; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine