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 diseaseMark 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 Conner11
Department of Neurosciences, University of California at San Diego, La Jolla, California
92093, USA. 2
Veterans Affairs Medical Center, San Diego, California
92161, USA. 3
Department of Surgery, University of California at San Diego, La Jolla, California
92093, USA. 4
Department of Surgery, Rush University Medical Center, Chicago, Illinois
60612, USA. 5
Department of Anesthesiology, University of California at San Diego, La Jolla, California
92093, USA. 6
Department of Neurology, University of California − Irvine, Irvine, California
92697, USA. 7
Departments of Anatomy and Neurobiology, University of California − Irvine, Irvine, California
92697, USA. 8
Department of Neurosciences, Rush University Medical Center, Chicago, Illinois
60612, USA.
Correspondence should be addressed to Mark H Tuszynski mtuszynski@ucsd.eduCholinergic 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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