Nerve growth factor expressed in the medial septum following in vivo gene delivery using a recombinant adeno-associated viral vector protects cholinergic neurons from fimbria-fornix lesion-induced degeneration

Nerve growth factor (NGF) has been shown to support the survival of axotomi zed medial septal cholinergic neurons after aspirative lesions of the fimbr ia-fornix (FF). This survival effect has been achieved utilizing intraventr icular and intraparenchymal delivery of the NGF protein, While the use of N GF for the treatment of the cholinergic deficits present in Alzheimer's dis ease shows promise based on its efficacy in animal models, concerns about s ide-effects of intraventricular NGF delivery in humans have been raised. In the present study, NGF was delivered directly to the medial septum via a r ecombinant adeno-associated viral vector (rAAV) encoding the cDNA for human NGF prior to a FF lesion in rats. This rAAV-mediated NGF delivery was show n to significantly attenuate the medial septal cholinergic cell loss observ ed in animals receiving an equivalent injection of a control rAAV vector. ( C) 1999 Academic Press.