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Letter

Nature Medicine 11, 551 - 555 (2005)
Published online: 24 April 2005 | doi:10.1038/nm1239

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

Mark H Tuszynski1,2, Leon Thal1,2, Mary Pay1, David P Salmon1, Hoi Sang U3, Roy Bakay4, Piyush Patel5, Armin Blesch1, H Lee Vahlsing1,2, Gilbert Ho1, Gang Tong1, Steven G Potkin6, James Fallon7, Lawrence Hansen1, Elliott J Mufson8, Jeffrey H Kordower8, Christine Gall7 & James Conner1

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.

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