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

Authors

Mark H. Tuszynski, Department of Neurosciences
Leon Thal, Department of Neurosciences
Mary Pay, Department of Neurosciences
David P. Salmon, Department of Neurosciences
Hoi Sang U, University of California, San Diego
Roy Bakay, Rush University Medical Center
Piyush Patel, University of California, San Diego
Armin Blesch, Department of Neurosciences
H. Lee Vahlsing, Department of Neurosciences
Gilbert Ho, Department of Neurosciences
Gang Tong, Department of Neurosciences
Steven G. Potkin, University of California, Irvine
James Fallon, University of California, Irvine
Lawrence Hansen, Department of Neurosciences
Elliott J. Mufson, Rush University Medical Center
Jeffrey H. Kordower, Rush University Medical Center
Christine Gall, University of California, Irvine
James Conner, Department of Neurosciences

Document Type

Article

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.

Publication Date

5-1-2005

Publication Title

Nature Medicine

ISSN

10788956

Volume

11

Issue

5

First Page

551

Last Page

555

PubMed ID

15852017

Digital Object Identifier (DOI)

10.1038/nm1239

Recommended Citation

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.
https://scholar.barrowneuro.org/neurobiology/1712