一项针对阿尔茨海默病的神经生长因子基因治疗的1期临床试验。

A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease.

作者信息

Tuszynski Mark H, Thal Leon, Pay Mary, Salmon David P, U Hoi Sang, Bakay Roy, Patel Piyush, Blesch Armin, Vahlsing H Lee, Ho Gilbert, Tong Gang, Potkin Steven G, Fallon James, Hansen Lawrence, Mufson Elliott J, Kordower Jeffrey H, Gall Christine, Conner James

机构信息

Department of Neurosciences, University of California at San Diego, La Jolla 92093, USA.

出版信息

Nat Med. 2005 May;11(5):551-5. doi: 10.1038/nm1239. Epub 2005 Apr 24.

DOI:10.1038/nm1239

PMID:15852017

Abstract

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.

摘要

胆碱能神经元丧失是阿尔茨海默病的主要特征。神经生长因子（NGF）可刺激胆碱能功能，改善记忆，并在损伤、淀粉样蛋白过度表达和衰老的动物模型中预防胆碱能变性。我们对8名轻度阿尔茨海默病患者进行了一项关于离体NGF基因递送的1期试验，将经基因改造以表达人NGF的自体成纤维细胞植入前脑。6名受试者平均随访22个月后，未出现NGF的长期不良反应。简易精神状态检查表和阿尔茨海默病评估量表-认知子分量表的评估表明认知衰退率有所改善。系列PET扫描显示治疗后皮质18-氟脱氧葡萄糖显著（P<0.05）增加。对一名受试者的脑尸检表明对NGF有强烈的生长反应。有必要对NGF治疗阿尔茨海默病进行更多的临床试验。