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多发性硬化症中的B细胞定向疗法。

B cell-directed therapies in multiple sclerosis.

作者信息

Gasperi Christiane, Stüve Olaf, Hemmer Bernhard

机构信息

Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675 München, Germany.

Departments of Neurology & Neurotherapeutics, University of Texas Southwestern Medical center, Dallas, TX, USA.

出版信息

Neurodegener Dis Manag. 2016;6(1):37-47. doi: 10.2217/nmt.15.67.

Abstract

Multiple sclerosis (MS) is a chronic inflammatory neurological disease of the CNS that goes along with demyelination and neurodegeneration. It is probably caused by an autoimmune response against the CNS, which emerges from the interplay of genetic and environmental factors. Although major progress has been made in the treatment of MS, it is still the leading cause for acquired nontraumatic neurological disability in young adults. Several therapeutic agents have been approved for the treatment of relapsing-remitting MS (RRMS), aiming at the reduction of relapses and a delay in disability progression. Three therapeutic monoclonal antibodies targeting CD20-positive B cells (rituximab, ocrelizumab and ofatumumab) were investigated in MRI-based Phase II and Phase III trials in RRMS, providing consistent evidence for a disease-ameliorating effect of B cell depleting therapies in MS. Here, we discuss the role of B cells and review current and future therapeutic approaches to target B cells in MS.

摘要

多发性硬化症(MS)是一种中枢神经系统的慢性炎性神经疾病,伴有脱髓鞘和神经变性。它可能由针对中枢神经系统的自身免疫反应引起,这种反应源于遗传和环境因素的相互作用。尽管在MS治疗方面已取得重大进展,但它仍是年轻成年人后天非创伤性神经残疾的主要原因。几种治疗药物已被批准用于治疗复发缓解型MS(RRMS),旨在减少复发并延缓残疾进展。在RRMS的基于MRI的II期和III期试验中,对三种靶向CD20阳性B细胞的治疗性单克隆抗体(利妥昔单抗、奥瑞珠单抗和奥法妥木单抗)进行了研究,为B细胞清除疗法对MS的疾病改善作用提供了一致证据。在此,我们讨论B细胞的作用,并综述目前和未来针对MS中B细胞的治疗方法。

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