RT期刊文章SR电子T1 RG3039的治疗效果在严重脊髓性肌肉萎缩症小鼠和正常人类志愿者(S25.003)摩根富林明神经病学神经学乔FD Lippincott Williams &威尔金斯SP S25.003 OP S25.003 VO 78是1补充A1 James Van Meerbeke A1首页丽贝卡·吉布斯A1 Heather泥水匠A1志华风林A1纯洁精神A1 Claribel凌晨A1 Bing夏A1文森特·雅克A1詹姆斯Rusche A1 Chien-Ping Ko A1夏洛特·萨姆纳年2012 UL //www.ez-admanager.com/content/78/1_Supplement/S25.003.abstract AB目的:探讨疗效的RG3039脊髓性肌萎缩(SMA)。背景脊髓性肌萎缩(SMA)是一种常染色体隐性遗传运动神经元疾病,经常导致早期死亡率。SMA是由纯合突变SMN2 SMN1基因和保留的,一个高度相似的SMN蛋白基因表达水平不足。目前没有疾病修饰治疗病人。反向SMN2拷贝数与疾病严重程度在人类和强劲增长SMN表达式防止SMA在老鼠身上。喹唑啉衍生物RG3039,增加SMN2启动子活动(加里奇et al ., 2005)和抑制清道夫开瓶酶又(辛格et al ., 2008)。设计/方法:严重的SMA老鼠接受0,3,或10毫克/公斤RG3039日报出生那天开始(P1)。行为、生化和组织学结果进行评估。第一阶段安全RG3039在健康志愿者的研究正在进行。结果:RG3039改善生存中值29%,最大体重达到了15%,和运动行为后果严重的SMA老鼠。这些影响是增加SMN2转录水平,改善神经肌肉接点(NMJ)形态学和生理学、增加肌肉和肌纤维面积和数量的增加vGluT1突触上腰椎运动神经元。临时健康志愿者的I期临床结果显示没有副作用药物接触抑制酶又完全循环PBMC。结论:RG3039改善生存、运动行为和运动单位结构和功能严重SMA老鼠。 Dosing in humans has produced no adverse effects to date. Phase I trials in SMA patients will be initiated in early 2012 and will represent the first clinical trial of a compound developed solely for the treatment of SMA.Supported by: Funding from the Repligen Corporation and grant support from the MDA, Families of Spinal Muscular Atrophy to CK and the National Institutes of Health (R01NS062869 to CJS).Disclosure: Dr. Van Meerbeke has nothing to disclose. Dr. Gibbs has nothing to disclose. Dr. Plasterer has received personal compensation for activities with Repligen Corporation as an employee. Dr. Feng has nothing to disclose. Dr. Lin has nothing to disclose. Dr. Wee has nothing to disclose. Dr. Xia has received personal compensation for activities with Repligen Corporation as an employee. Dr. Jacques has received personal compensation for activities with Repligen Corporation as an employee. Dr. Rusche has received personal compensation for activities with Repligen Corporation as an employee. Dr. Ko has nothing to disclose. Dr. Sumner has nothing to disclose.Wednesday, April 25 2012, 14:00 pm-15:45 pm