TY - T1的初步证据的药效学影响RG7916珠宝鱼,脊髓性肌肉萎缩症患者的一项研究曾参与一项研究与另一个SMN2-Splicing靶向治疗(S46.003) JF -神经学乔-神经学六世- 90 - 15补充SP - S46.003盟克劳迪娅奇盟Eugenio麦克利克劳斯盟盟-德克费舍尔盟多米尼克-莫妮卡亚历山大盟吉莉安·阿姆斯特朗盟Heidemarie Kletzl AU -玛丽安戈贝尔盟弓佳盟- Tobias Bergauer盟Ksenija Gorni AU 首页-奥马尔哈Y1 - 2018/04/10 UR - //www.ez-admanager.com/content/90/15_Supplement/S46.003.abstract N2 -目的:珠宝鱼(NCT03032172)是一种探索性,开放研究建立安全、耐受性和药代动力学(PK) RG7916病人曾参与一项研究与治疗目标运动神经元的生存2 (SMN2)信使rna剪接。背景:脊髓性肌萎缩(SMA)是一种罕见的遗传性神经肌肉疾病引起的SMN1基因的功能丧失。虽然SMN1全长SMN蛋白产生,第二个基因,SMN2,产生低水平的功能性SMN蛋白由于可变剪接SMN2 pre-mRNA。RG7916口头管理,中央和周边地分布式SMN2 pre-mRNA拼接修饰符增加SMN蛋白水平。设计/方法:珠宝鱼是一个多中心、非盲、探索性研究评估安全性、耐受性和PK的日常口腔RG7916 SMA患者类型2或3,12-60岁,曾参与一项研究与治疗目标SMN2拼接。药效学(PD)影响SMN2 mRNA和SMN蛋白也评估。结果:在抽象的提交,8例收到RG7916 32周。到目前为止,RG7916安全和耐受性良好,没有毒品安全发现导致在任何SMA患者暴露于RG7916撤军。初步PD RG7916治疗后数据显示快速增加全身SMN2 (SMN2FL) / SMNΔ7 mRNA比治疗后发作,和增加到4倍基线超过4周。这SMN2FL / SMNΔ7 mRNA比率增加导致了多达4倍SMN蛋白增加超过4周。一个珠宝鱼更新将包括安全性和可用的生物标记数据。结论:珠宝鱼目前招聘网站在欧洲和美国。 Together with the ongoing SUNFISH (SMA Type 2 and 3) and FIREFISH (SMA Type 1) studies, JEWELFISH will provide valuable insights into the safety, tolerability, PK and PD of daily oral RG7916.Study Supported by:Sponsored by F. Hoffmann-La RocheDisclosure: Dr Chiriboga has nothing to disclose. Dr. Mercuri has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen MA, Inc, Ionis Pharmaceuticals, Inc. & F. Hoffman La-Roche Ltd. Dr. Fischer has nothing to disclose. Dr. Kraus has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche. Dr. Alexander has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche. Dr. Armstrong has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche. Dr. Kletzl has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche. Dr. Kletzl holds stock and/or stock options in Roche. Dr. Kletzl has received research support from Roche. Dr. Gerber has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche. Dr. Gerber holds stock and/or stock options in Roche. Dr. Cleary has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F.Hoffmann-La Roche. Dr. Bergauer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche. Dr. Gorni has nothing to disclose. Dr. Khwaja has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche. Dr. Khwaja holds stock and/or stock options in Roche, which sponsored research in which Dr. Khwaja was involved as an investigator. Dr. Khwaja has received research support from Roche. ER -