Patisiran, RNAi治疗遗传性转体基因淀粉样变。
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亚当斯D, Gonzalez-Duarte baillie gifford WD,杨CC,建筑师,克里斯汀AV, Tournev我,施密特HH,科埃略T,伯克杰,林KP,维塔克,Attarian年代,Plante-Bordeneuve V, Mezei MM, Campistol JM, Buades J, Brannagan TH 3日,金正日BJ,哦,J, Parman Y, Sekijima Y,霍金斯PN,所罗门SD Polydefkis M,戴克PJ,甘地PJ Goyal年代,陈J, Strahs, Nochur SV,糖果山,加戈PP、Vaishnaw AK, Gollob是的,Suhr OB
Patisiran, RNAi治疗遗传性转体基因淀粉样变。
郑传经地中海J。2018年7月5日,379(1):乳。doi: 10.1056 / NEJMoa1716153。
- PubMed ID
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29972753 (在PubMed]
- 文摘
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背景:Patisiran,临床实验的RNA干扰治疗代理,特别是抑制肝合成转体基因。方法:在这个阶段3的试验中,我们随机遗传转体基因淀粉样变患者多神经病,在2:1的比例,接受静脉注射patisiran(0.3毫克/公斤体重)或安慰剂每隔3周。主要终点是基线的变更修改神经病变损伤评分+ 7 (mNIS + 7;范围,0到304,得分越高表明更多的障碍)在18个月。其他评估包括Life-Diabetic神经病变(诺福克QOL-DN)的诺福克质量问卷(范围,4 - 136,得分越高表明糟糕的生活质量),走十米级测试与步速测量(米/秒),和修改体重指数(BMI,修改定义为(用体重(公斤)除以身高(米)的平方克每升xalbumin水平;较低的值表示营养状况更糟)。结果:共有225名患者进行了随机化(148到77 patisiran组和安慰剂组)。均值(+ / -标准差)mNIS + 7 patisiran组的基线是80.9 + / - -41.5和74.6 + / - -37.0在安慰剂组;最小二乘均值从基线(+ /硒)变化是-6.0 + / - -1.7和28.0 + / - -2.6(差异,-34.0分;在18个月P < 0.001)。 The mean (+/-SD) baseline Norfolk QOL-DN score was 59.6+/-28.2 in the patisiran group and 55.5+/-24.3 in the placebo group; the least-squares mean (+/-SE) change from baseline was -6.7+/-1.8 versus 14.4+/-2.7 (difference, -21.1 points; P<0.001) at 18 months. Patisiran also showed an effect on gait speed and modified BMI. At 18 months, the least-squares mean change from baseline in gait speed was 0.08+/-0.02 m per second with patisiran versus -0.24+/-0.04 m per second with placebo (difference, 0.31 m per second; P<0.001), and the least-squares mean change from baseline in the modified BMI was -3.7+/-9.6 versus -119.4+/-14.5 (difference, 115.7; P<0.001). Approximately 20% of the patients who received patisiran and 10% of those who received placebo had mild or moderate infusion-related reactions; the overall incidence and types of adverse events were similar in the two groups. CONCLUSIONS: In this trial, patisiran improved multiple clinical manifestations of hereditary transthyretin amyloidosis. (Funded by Alnylam Pharmaceuticals; APOLLO ClinicalTrials.gov number, NCT01960348 .).
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