Cationic lipid-mediated CFTR gene transfer to the lungs and nose of patients with cystic fibrosis:: a double-blind placebo-controlled trial
Cationic lipid-mediated CFTR gene transfer to the lungs and nose of patients with cystic fibrosis:: a double-blind placebo-controlled trial
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DOI：
10.1016/s0140-6736(98)06532-5
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发表时间：
1999-03-20
期刊：
影响因子：
168.9
通讯作者：
Geddes, DM
中科院分区：
文献类型：
--
作者：
Alton, EWFW;Stern, M;Geddes, DM
背景：我们和其他人以前报道过，在阳离子-脂质介导下将囊性纤维化跨膜传导调节因子(CFTR)基因转移到囊性纤维化患者的鼻黏膜上皮后，氯离子转运发生了显著变化。在一项双盲安慰剂对照试验中，我们研究了这种基因转移到囊性纤维化患者肺和鼻子的安全性和有效性。方法8名囊性纤维化患者被随机分配到肺内雾化吸入DNA-脂质复合体(活性)，一周后鼻腔给药。8名对照组患者遵循相同的方案，但只服用脂类药物(安慰剂)。安全性通过临床、X线片、肺功能、诱导痰和组织学分析进行评估。通过分析载体特异性CFTRDNA和mRNA、体内电势差、氯离子外排的荧光分析和细菌黏附来评估疗效。结果8名接受活性复合体的患者中有7名报告了轻度流感样症状，并在36小时内消失。8名接受活性复合体和安慰剂组的8名患者中有6名在肺部给药后12小时内报告了轻度呼吸道症状。这两个事件都不需要特殊的治疗。肺部给药导致显著(p
Background We and others have previously reported significant changes in chloride transport after cationic-lipid-mediated transfer of the cystic fibrosis transmembrane conductance regulator (CFTR) gene to the nasal epithelium of patients with cystic fibrosis. We studied the safety and efficacy of this gene transfer to the lungs and nose of patients with cystic fibrosis in a double-blind placebo-controlled trial.Methods Eight patients with cystic fibrosis were randomly assigned DNA-lipid complex (active) by nebulisation into the lungs followed 1 week later by administration to the nose. Eight control patients followed the same protocol but with the lipid alone (placebo). Safety was assessed clinically, by radiography, by pulmonary function, by induced sputum, and by histological analysis. Efficacy was assessed by analysis of vector-specific CFTR DNA and mRNA, in-vivo potential difference, epifluorescence assay of chloride efflux, and bacterial adherence.Findings Seven of the eight patients receiving the active complex reported mild influenza-like symptoms that resolved within 36 h. Six of eight patients in both the active and placebo groups reported mild airway symptoms over a period of 12 h following pulmonary administration. No specific treatment was required for either event. Pulmonary administration resulted in a significant (p