Omaveloxolone治疗Friedreich共济失调的研究进展  

Research progress of Omaveloxolone in treatment of Friedreich′s ataxia

作　　者：卞婷婷 何心 BIAN Tingting;HE Xin(Department of Pharmacy,Yangzhou Maternal and Child Health Care Hospital Affliated to Yangzhou University,Jiangsu Province,Yangzhou225000,China;Department of Pharmacy,Women's Hospital of Nanjing Medical University,Nanjing Maternity and Child Health Care Hospital,Jiangsu Province,Nanjing210004,China)

机构地区：[1]扬州大学医学院附属扬州妇幼保健院药学部,江苏扬州225000 [2]南京医科大学附属妇产医院南京市妇幼保健院药学部,江苏南京210004

出　　处：《中国当代医药》2024年第17期189-192,共4页China Modern Medicine

摘　　要：Omaveloxolone于2023年2月由美国食品药品监督管理局(FDA)正式批准用于成人和16岁及以上青少年Friedreich共济失调(FRDA)的治疗。Omaveloxolone是第一种也是唯一一种适用于FRDA患者的药物。Omaveloxolone已获得美国FDA的“孤儿药”、快速通道和罕见儿科疾病称号,以及欧洲委员会的“孤儿药”称号。FRDA是一种极其罕见的神经肌肉疾病,是一种遗传性疾病,由编码共济蛋白的frataxin(FXN)基因突变引起。在FRDA患者中核因子E2相关因子2(Nrf2)信号传导是被抑制的,而Omaveloxolone可通过抑制Kelch样ECH关联蛋白1(KEAP1)阻止Nrf2泛素化从而激活Nrf2,通过激活Nrf2发挥修复线粒体功能、降低氧化应激、抑制促炎信号等作用。因此Omaveloxolone可改善FRDA患者的神经功能,减缓患者的疾病进展。现对其作用机制、药效学、药代动力学、临床研究及安全性等作一介绍。Omaveloxolone was officially approved by the U.S.Food and Drug Administration(FDA)in February 2023 for the treatment of Friedreich's ataxia(FRDA)in adults and adolescents 16 years and older.Omaveloxolone has received“orphan drug”,fast track and rare pediatric disease designation from the FDA,as well as“orphan drug”designation from the European Commission.FRDA is an extremely rare neuromuscular disorder that is an inherited disorder caused by mutations in the frataxin(FXN)gene that encodes the protein ataxin.Nuclear factor E2 associated factor 2(Nrf2)signaling is inhibited in FRDA patients,and Omaveloxolone inhibits Nrf2 ubiquitination by inhibiting Kelch-like ECH associated protein 1(KEAP1),thereby activating Nrf2.By activating Nrf2,it can repair mitochondrial function,reduce oxidative stress and inhibit pro-inflammatory signal.Therefore,Omaveloxolone improves neurological function and slows disease progression in patients with FRDA.The mechanism of action,pharmacodynamics,pharmacokinetics,clinical studies and safety were reviewed.

关 键 词：Omaveloxolone FRIEDREICH共济失调 核因子E2相关因子2 研究进展 

分 类 号：R741[医药卫生—神经病学与精神病学]