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

Nat Med. 2005 May;11(5):551-5. doi: 10.1038/nm1239. Epub 2005 Apr 24.


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 types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Alzheimer Disease / therapy*
  • Cholinergic Fibers / metabolism*
  • Cognition / physiology
  • Fibroblasts / metabolism
  • Fluorodeoxyglucose F18 / metabolism
  • Genetic Therapy / methods*
  • Histological Techniques
  • Humans
  • Middle Aged
  • Nerve Growth Factor / genetics
  • Nerve Growth Factor / metabolism
  • Nerve Growth Factor / therapeutic use*
  • Neuropsychological Tests
  • Positron-Emission Tomography
  • Prosencephalon / metabolism
  • Prosencephalon / pathology
  • Prosencephalon / surgery*


  • Fluorodeoxyglucose F18
  • Nerve Growth Factor