A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease
A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease
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DOI：
10.1038/nm1239
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发表时间：
2005-05-01
期刊：
影响因子：
82.9
通讯作者：
Conner, J
中科院分区：
文献类型：
--
作者：
Tuszynski, MH;Thal, L;Conner, J
胆碱能神经元丢失是阿尔茨海默病的主要特征。神经生长因子（NGF）在损伤、淀粉样蛋白过度表达和衰老的动物模型中刺激胆碱能功能，改善记忆并防止胆碱能变性。我们在8名轻度阿尔茨海默病患者中进行了离体NGF基因递送的1期试验，将经遗传修饰以表达人NGF的自体成纤维细胞植入前脑。在6名受试者平均随访22个月后，没有发生NGF的长期不良反应。简易精神状态检查和阿尔茨海默病评估量表-认知子成分的评估表明认知下降率有所改善。连续PET扫描显示治疗后皮质18-氟脱氧葡萄糖显著增加（P < 0.05）。一名受试者的脑尸检表明对NGF有强烈的生长反应。神经生长因子治疗阿尔茨海默病的其他临床试验是必要的。
Cholinergic neuron loss is a cardinal feature of Alzheimer disease. Nerve growth factor (NGF) stimulates cholinergic function, improves memory and prevents cholinergic degeneration in animal models of injury, amyloid overexpression and aging. We performed a phase 1 trial of ex vivo NGF gene delivery in eight individuals with mild Alzheimer disease, implanting autologous fibroblasts genetically modified to express human NGF into the forebrain. After mean follow-up of 22 months in six subjects, no long-term adverse effects of NGF occurred. Evaluation of the Mini-Mental Status Examination and Alzheimer Disease Assessment Scale-Cognitive subcomponent suggested improvement in the rate of cognitive decline. Serial PET scans showed significant (P < 0.05) increases in cortical 18-fluorodeoxyglucose after treatment. Brain autopsy from one subject suggested robust growth responses to NGF. Additional clinical trials of NGF for Alzheimer disease are warranted.