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

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

Research output: Contribution to journalArticlepeer-review

902 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)551-555
Number of pages5
JournalNature Medicine
Issue number5
StatePublished - May 2005
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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