单克隆抗体:多发性硬化症的靶向治疗。

Lorena Lorefice, Giuseppe Fenu, Jessica Frau, Giancarlo Coghe, Maria Giovanna Marrosu
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引用次数: 4

摘要

多发性硬化(MS)是一种复杂的中枢神经系统自身免疫性疾病。它的特点是导致神经轴突损伤的促炎和神经退行性过程。在过去的二十年中,广泛的免疫调节和免疫抑制治疗已被用于多发性硬化症的治疗,几种治疗方法已被开发或正在评估中,以减少复发、疾病进展和多发性硬化症相关的长期残疾。最近,人们越来越关注具有选择性作用的治疗方法,特别是单克隆抗体,以靶向MS中涉及的几种生物途径。迄今为止,只有Natalizumab (Tysabri(®))被批准用于治疗活性MS形式。其治疗机制是阻断许多白细胞的a4-整合素分子,导致免疫细胞迁移减少,特别是淋巴细胞穿过血脑屏障。此外,其他有希望的分子正在临床试验中研究。在这篇综述中,我们总结和讨论了单克隆抗体的历史,药效学和安全性,已批准或正在评估选择性治疗多发性硬化症。
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Monoclonal antibodies: a target therapy for multiple sclerosis.

Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system. It is characterized by a proinflammatory and neurodegenerative process that results in neuroaxonal damage. Over the last two decades, a wide range of immunomodulatory and immunosuppressive treatments have been used for the management of MS. Several treatments have been developed or are under evaluation for reducing relapses, disease progression and long-term MS-related disability. Recently, a growing interest has emerged for therapeutics with very selective actions, particularly monoclonal antibodies, to target several biological pathways involved in MS. To date, only Natalizumab (Tysabri(®)) has been approved for the treatment of active MS forms. Its therapeutic mechanism is the blockade of the a4-integrin molecule of many leukocytes, which leads to a decrease of immune cells migration, in particular of lymphocytes, across the blood-brain barrier. Furthermore, other promising molecules are under study in clinical trials. In this review, we summarize and discuss the history, pharmacodynamics and safety of monoclonal antibodies that have been approved or are under evaluation for the selective treatment of MS.

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