Fontoura Paulo, Garren Hideki
Roche Pharmaceuticals, CNS Translational Medicine Group, Basel, Switzerland.
Results Probl Cell Differ. 2010;51:259-85. doi: 10.1007/400_2010_36.
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.
从很多方面来看,目前用于治疗多发性硬化症(MS)的方法并不令人满意。最初的干扰素-β疗法并非一定基于对该疾病病理生理机制的广泛了解。随着对MS自身免疫机制,尤其是所涉及的分子靶点有了越来越深入的认识,出现了几种治疗方法。在本章中,我们将重点介绍一些有前景的临床前方法以及后期临床试验中的疗法,这些都是由于对MS分子病理生理学有了更好的理解而研发出来的。这些处于临床阶段的疗法包括口服药物、单克隆抗体和抗原特异性疗法。当已知分子靶点以及出现任何安全问题时,我们会特别加以强调,因为尽管需要提高疗效,但MS仍然是一种任何药物的安全性都至关重要的疾病。