Nerve growth factor (NGF) is a 13,000 kilodalton trophic factor shown to preserve the function of cholinergic neurons in both rodent and nonhuman primate lesion studies. It is postulated that NGF may benefit Alzheimer's patients by preventing degeneration of cholinergic cell populations. Somatic gene therapy with delivery of NGF via transfected fibroblasts can be an effective site specific delivery system for this neurotrophic factor. Two primary areas of focus in 1994 were long term studies of graft survival in young adult rhesus macaques, with unilateral lesions of the fornix and the effects of NGF grafts in aged (19 years<) behaviorally characterized rhesus macaques. For the first study two young rhesus received NGF grafts and two received B-gal control grafts. One of each will be sacrificed at six months and one year to assess graft survival. For the second study the population consisted of eight aged rhesus; two were dropped from the study for health reasons. Six animals then entered a two month program of behavioral assessment of memory utilizing a delayed response test to assess memory and cognition in nonhuman primates. Completing the behavioral testing, the animals were imaged with MRI and PET as part of a related project, and underwent a neurosurgical procedure involving intracerebral injection of autologous fibroblasts collected from the skin earlier. Three animals received fibroblasts containing the human gene for NGF. The remaining three received fibroblasts containing a ~ galactosidase marker gene. Three weeks post-operatively behavioral testing was repeated to see if the NGF animals demonstrated improved performance over the aged control group. Following testing the animals had repeat imaging, followed by euthanasia and histological evaluation of the grafts and neuronal cell populations in the target site, the nucleus basalis. Evaluation of both behavioral results and histology from this study population is underway.
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