Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomised, controlled trial
Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomised, controlled trial
复制标题
DOI：
10.1016/s1474-4422(10)70254-4
复制
发表时间：
2010-12-01
期刊：
影响因子：
48
通讯作者：
Olanow, C. Warren
中科院分区：
文献类型：
--
作者：
Marks, William J., Jr.;Bartus, Raymond T.;Olanow, C. Warren
背景在开放标签阶段1试验中，通过腺相关2型载体(AAV2)转导营养因子神经妥林的耐受性良好，似乎可以改善晚期帕金森病患者的运动功能。我们的目标是在双盲2期随机试验中评价AAV2Neurturin的安全性和有效性。方法我们在晚期帕金森病患者中进行了一项多中心双盲假手术对照试验，由中央计算机生成的随机代码随机分配(21)接受AAV2Neurturin(5 4x10(11)载体基因组)双侧壳核注射或假手术，所有患者和研究人员除神经外科手术组外均被蒙蔽在进行治疗分配时，主要终点是帕金森S病统一评定量表的运动评分从基线改变到12个月，在实际定义的关闭状态下，所有在基线后至少有一次评估的随机分配的患者都进入了初步分析。这项试验在临床试验GOV NCT00400634上登记。结果2006年12月至2008年11月期间，来自美国9个地点的58名患者参加了试验。与对照组相比，接受AAV2Neurturin治疗的患者的主要终点没有显著差异(差异0 31[SE 2 63]95%CI 5 58至4 97 p=0 91)在38名接受AAV2NURURURIN治疗的患者和20名对照组中的4名患者中，AAV2NURURURIN组有3名患者和假手术组有2名患者发生肿瘤。12个月后使用UPDRS运动评分进行评估时，解释性AAV2NURURTIN并不优于假手术，但通过额外靶向黑质和长期随访的可能性应在进一步研究中进行调查。
Background In an open label phase 1 trial, gene delivery of the trophic factor neurturin via an adeno associated type 2 vector (AAV2) was well tolerated and seemed to improve motor function m patients with advanced Parkinson's disease We aimed to assess the safety and efficacy of AAV2 neurturin in a double blind phase 2 randomised trialMethods We did a multicentre double blind sham surgery controlled trial in patients with advanced Parkinson s disease Patients were randomly assigned (21) by a central computer generated randomisation code to receive either AAV2 neurturin (5 4x10(11) vector genomes) injected bilaterally into the putamen or sham surgery All patients and study personnel with the exception of the neurosurgical team were masked to treatment assignment The primary endpoint was change from baseline to 12 months in the motor subscore of the unified Parkinson s disease rating scale in the practically defined off state All randomly assigned patients who had at least one assessment after baseline were included in the primary analyses This trial is registered at ClinicalTrials gov NCT00400634Results Between December 2006 and November 2008 58 patients from nine sites in the USA participated in the trial There was no significant difference in the primary endpoint in patients treated with AAV2 neurturin compared with control individuals (difference 0 31 [SE 2 63] 95% CI 5 58 to 4 97 p=0 91) Serious adverse events occurred in 13 of 38 patients treated with AAV2 neurturin and four of 20 control individuals Three patients in the AAV2 neurturin group and two in the sham surgery group developed tumoursInterpretation Intraputaminal AAV2 neurturin is not superior to sham surgery when assessed using the UPDRS motor score at 12 months However the possibility of a benefit with additional targeting of the substantia nigra and longer term follow up should be investigated in further studiesFunding Ceregene and Michael J Fox Foundation for Parkinson s Research