Pharmacological Profile of Viltolarsen for the Treatment of Duchenne Muscular Dystrophy: A Japanese Experience.

IF 3.1 Q2 PHARMACOLOGY & PHARMACY
Clinical Pharmacology : Advances and Applications Pub Date : 2021-12-16 eCollection Date: 2021-01-01 DOI:10.2147/CPAA.S288842
Rohini Roy Roshmi, Toshifumi Yokota
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引用次数: 9

Abstract

Duchenne muscular dystrophy (DMD) is a fatal, X-linked recessive disorder characterized by progressive muscle loss and cardiorespiratory complications. Mutations in the DMD gene that eliminate the production of dystrophin protein are the underlying causes of DMD. Viltolarsen is a drug of phosphorodiamidate morpholino oligomer (PMO) chemistry, designed to skip exon 53 of the DMD gene. It aims to produce truncated but partially functional dystrophin in DMD patients and restore muscle function. Based on a preclinical study showing the ability of antisense PMOs targeting the DMD gene to improve muscle function in a large animal model, viltolarsen was developed by Nippon Shinyaku and the National Center of Neurology and Psychiatry in Japan. Following clinical trials conducted in Japan, Canada, and the United States showing significant improvements in muscle function, viltolarsen was approved for medical use in Japan in March 2020 and the United States in August 2020, respectively. Viltolarsen is a mutation-specific drug and will work for 8% of the persons with DMD who carry mutations amenable to exon 53 skipping. This review summarizes the pharmacological profile of viltolarsen, important clinical trials, and challenges, focusing on the contribution of Japanese patients and researchers in its development.

Abstract Image

Abstract Image

维托拉森治疗杜氏肌营养不良的药理学特征:日本经验。
杜氏肌营养不良症(DMD)是一种致命的x连锁隐性疾病,以进行性肌肉丧失和心肺并发症为特征。DMD基因的突变消除了肌营养不良蛋白的产生,这是DMD的潜在原因。Viltolarsen是一种磷酸二酯morpholino oligomer (PMO)化学药物,旨在跳过DMD基因的53外显子。它的目的是在DMD患者中产生截断但部分功能的肌营养不良蛋白,并恢复肌肉功能。viltolarsen是由Nippon Shinyaku和日本国家神经病学和精神病学中心开发的,基于一项临床前研究显示,针对DMD基因的反义PMOs能够改善大型动物模型的肌肉功能。在日本、加拿大和美国进行的临床试验显示,viltolarsen在肌肉功能方面有显著改善,并于2020年3月和2020年8月分别在日本和美国获得医疗用途批准。Viltolarsen是一种突变特异性药物,将对8%携带外显子53跳变的突变的DMD患者起作用。本文综述了viltolarsen的药理学概况、重要的临床试验和面临的挑战,重点介绍了日本患者和研究人员在其开发中的贡献。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.60
自引率
0.00%
发文量
14
审稿时长
16 weeks
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