title: A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease.
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.
authors.affiliation: Department of Neurosciences, University of California at San Diego, La Jolla 92093, USA. mtuszynski@ucsd.edu <mtuszynski@ucsd.edu>
authors.forename: Mark H
authors.initials: MH
authors.lastname: Tuszynski
authors.forename: Leon
authors.initials: L
authors.lastname: Thal
authors.forename: Mary
authors.initials: M
authors.lastname: Pay
authors.forename: David P
authors.initials: DP
authors.lastname: Salmon
authors.forename: Hoi Sang
authors.initials: HS
authors.lastname: U
authors.forename: Roy
authors.initials: R
authors.lastname: Bakay
authors.forename: Piyush
authors.initials: P
authors.lastname: Patel
authors.forename: Armin
authors.initials: A
authors.lastname: Blesch
authors.forename: H Lee
authors.initials: HL
authors.lastname: Vahlsing
authors.forename: Gilbert
authors.initials: G
authors.lastname: Ho
authors.forename: Gang
authors.initials: G
authors.lastname: Tong
authors.forename: Steven G
authors.initials: SG
authors.lastname: Potkin
authors.forename: James
authors.initials: J
authors.lastname: Fallon
authors.forename: Lawrence
authors.initials: L
authors.lastname: Hansen
authors.forename: Elliott J
authors.initials: EJ
authors.lastname: Mufson
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Kordower
authors.forename: Christine
authors.initials: C
authors.lastname: Gall
authors.forename: James
authors.initials: J
authors.lastname: Conner
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D002799:Cholinergic Fibers / Q000378:metabolism*; D003071:Cognition / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D006652:Histological Techniques; D006801:Humans; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D016548:Prosencephalon / Q000378:metabolism / Q000473:pathology / Q000601:surgery*
chemical_list: D019788:Fluorodeoxyglucose F18; D020932:Nerve Growth Factor