Nerve growth factor (NGF) has been shown in vitro and in vivo to support the growth of basal forebrain cholinergic neurons. In Alzheimer's Disease, these cells undergo significant degenerative changes which may be responsible for the cognitive and memory deficits associated with this disorder. Because of this correlation, NGF has been proposed as a therapeutic for the treatment of Alzheimer's Disease. However, the use of NGF as a therapeutic is hampered by the lack of a noninvasive means of delivering the compound to the brain. It is the goal of this proposal to demonstrate that a carrier-based drug delivery system can be used for the effective transport of NGF from the bloodstream to the brain parenchyma. This delivery system utilizes, as carrier molecules, monoclonal antibodies that bind to the transferrin receptor, which is found in abundance on the luminal surface of brain capillary endothelial cells, and undergo transcytosis across the blood-brain barrier via their interaction with the receptor. It was demonstrated during Phase I of this project that NGF could be conjugated in a biologically active form to the carrier antibody. The in vivo efficacy of the NGF delivered using this system will be examined during Phase II.
