PT -期刊文章盟James Van Meerbeke AU -丽贝卡·吉布斯盟冯-希瑟泥水匠盟志华盟-林纯洁精神盟Claribel凌晨AU - Bing夏盟文森特·雅克AU -詹姆斯Rusche盟Chien-Ping Ko AU -夏洛特·萨姆纳TI - RG3039严重脊髓性肌肉萎缩症的治疗影响小鼠和正常人类志愿者(S25.003) DP - 2012年4月25日TA -神经病学PG - S25.003 S25.003 VI - 78 IP - 1补充4099 - //www.ez-admanager.com/content/78/1_Supplement/S25.003.short 4100 - //www.ez-admanager.com/content/78/1_Supplement/S25.003.full所以Neuro首页logy2012 4月25日;78 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。 These effects are associated with increased SMN2 transcript levels, improved neuromuscular junction (NMJ) morphology and physiology, increased muscle and myofiber area, and increased number of vGluT1 synapses onto lumbar motor neurons. Interim phase I clinical results in healthy volunteers indicate no adverse effects at drug exposure that inhibits DcpS enzyme completely in circulating PBMC.Conclusions: RG3039 improves survival, motor behavior, and motor unit structure and function in severe SMA mice. 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