A phase1 study of stereotactic gene delivery of AAV2-NGF for Alzheimer's disease

Alzheimers Dement. 2014 Sep;10(5):571-81. doi: 10.1016/j.jalz.2013.09.004. Epub 2014 Jan 7.


Background: Nerve growth factor (NGF) is an endogenous neurotrophic-factor protein with the potential to restore function and to protect degenerating cholinergic neurons in Alzheimer's disease (AD), but safe and effective delivery has proved unsuccessful.

Methods: Gene transfer, combined with stereotactic surgery, offers a potential means to solve the long-standing delivery obstacles. An open-label clinical trial evaluated the safety and tolerability, and initial efficacy of three ascending doses of the genetically engineered gene-therapy vector adeno-associated virus serotype 2 delivering NGF (AAV2-NGF [CERE-110]). Ten subjects with AD received bilateral AAV2-NGF stereotactically into the nucleus basalis of Meynert.

Results: AAV2-NGF was safe and well-tolerated for 2 years. Positron emission tomographic imaging and neuropsychological testing showed no evidence of accelerated decline. Brain autopsy tissue confirmed long-term, targeted, gene-mediated NGF expression and bioactivity.

Conclusions: This trial provides important evidence that bilateral stereotactic administration of AAV2-NGF to the nucleus basalis of Meynert is feasible, well-tolerated, and able to produce long-term, biologically active NGF expression, supporting the initiation of an ongoing multicenter, double-blind, sham-surgery-controlled trial.

Keywords: Cholinergic neurons; Gene therapy; Nerve growth factor; Neuroprotection; Neurorestoration; Neurotrophic factors; Nucleus basalis of Meynert; Translational R&D.

Publication types

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

MeSH terms

  • Aged
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Alzheimer Disease / therapy*
  • Basal Nucleus of Meynert
  • Dependovirus / genetics*
  • Feasibility Studies
  • Female
  • Genetic Therapy / methods*
  • Genetic Vectors
  • Humans
  • Immunohistochemistry
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Nerve Growth Factor / genetics*
  • Neuropsychological Tests
  • Neurosurgical Procedures
  • Positron-Emission Tomography
  • Stereotaxic Techniques
  • Treatment Outcome


  • NGF protein, human
  • Nerve Growth Factor