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

被引：772

作者：

Tuszynski, MH ^{[1
]}

Thal, L

Pay, M

Salmon, DP

Sang, UH

Bakay, R

Patel, P

Blesch, A

Vahlsing, HL

Ho, G

Tong, G

Potkin, SG

Fallon, J

Hansen, L

Mufson, EJ

Kordower, JH

Gall, C

Conner, J

机构：

[1] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA

[2] Vet Affairs Med Ctr, San Diego, CA 92161 USA

[3] Univ Calif San Diego, Dept Surg, La Jolla, CA 92093 USA

[4] Rush Univ, Med Ctr, Dept Surg, Chicago, IL 60612 USA

[5] Univ Calif San Diego, Dept Anesthesiol, La Jolla, CA 92093 USA

[6] Univ Calif Irvine, Dept Neurol, Irvine, CA 92697 USA

[7] Univ Calif Irvine, Dept Anat & Neurobiol, Irvine, CA 92697 USA

[8] Rush Univ, Med Ctr, Dept Neurosci, Chicago, IL 60612 USA

来源：

NATURE MEDICINE | 2005年 / 11卷 / 05期

关键词：

D O I：

10.1038/nm1239

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：551 / 555

页数：5

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