A phase1 study of stereotactic gene delivery of AAV2-NGF for Alzheimer's disease - PubMed (original) (raw)

Clinical Trial

doi: 10.1016/j.jalz.2013.09.004. Epub 2014 Jan 7.

Tiffany L Baumann 2, Roy A E Bakay 3, Jeffrey M Ostrove 2, Joao Siffert 2, Adam S Fleisher 1, Christopher D Herzog 2, David Barba 1, Mary Pay 1, David P Salmon 1, Yaping Chu 3, Jeffrey H Kordower 3, Kathie Bishop 2, David Keator 4, Steven Potkin 4, Raymond T Bartus 5

Affiliations

Clinical Trial

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

Michael S Rafii et al. Alzheimers Dement. 2014 Sep.

Abstract

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.

Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

PubMed Disclaimer

Publication types

MeSH terms

Substances

LinkOut - more resources