A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease
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.
Digital Object Identifier (DOI)
Tuszynski, Mark H.; Thal, Leon; Pay, Mary; Salmon, David P.; Sang U, Hoi; 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; and Conner, James, "A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease" (2005). Translational Neuroscience. 1712.