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

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

Author information

1
Department of Neurosciences, University of California, San Diego, CA, USA.
2
Ceregene, Inc., San Diego, CA, USA.
3
Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
4
University of California, Irvine, CA, USA.
5
Ceregene, Inc., San Diego, CA, USA. Electronic address: bartus@rtbioconsultants.com.

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

PMID:
24411134
DOI:
10.1016/j.jalz.2013.09.004
[Indexed for MEDLINE]

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