A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease |
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| Authors: | 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 |
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| Institution: | Department of Neurosciences, University of California at San Diego, La Jolla 92093, USA. mtuszynski@ucsd.edu |
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| 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. |
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