Alzheimer's disease (AD) is characterized by degeneration and loss of neurons and synapses throughout the brain, causing the progressive decline in cognitive function leading to
dementia. No effective treatment is currently available.
Nerve growth factor (
NGF)
therapy has been proposed as a potential treatment of preventing degeneration of basal forebrain cholinergic neurons in AD. In a previous study, AD patient's own fibroblasts genetically modified to produce
NGF were transplanted directly into the brain and protected cholinergic neurons from degeneration and improved cognitive function in AD patients. In the present study, human neural stem cells (NSCs) are used in place of fibroblasts to deliver
NGF in
ibotenic acid-induced learning-deficit rats. Intrahippocampal injection of
ibotenic acid caused severe neuronal loss, resulting in learning and
memory deficit.
NGF protein released by F3.
NGF human NSCs in culture medium is 10-fold over the control F3 naive NSCs at 1.2 µg/10(6) cells/day. Overexpression of
NGF in F3.
NGF cells induced improved survival of NSCs from
cytotoxic agents H2O2, Aβ, or
ibotenic acid in vitro. Intrahippocampal
transplantation of F3.
NGF cells was found to express
NGF and fully improved the learning and memory function of
ibotenic acid-challenged animals. Transplanted F3.
NGF cells were found all over the brain and differentiated into neurons and astrocytes. The present study demonstrates that human NSCs overexpressing
NGF improve cognitive function of learning-deficit model mice.