This research is to test implementation of a non-invasive method for site-specific delivery of growth factors to the traumatically injured brain. Various neurotrophins including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and insulin like growth factor (IGF-1) have been shown to significantly attenuate neuronal cell loss and behavioral deficits associated with traumatic brain injury (TBI). Neurotrophins have not been developed as treatments in humans because of the significant side effects encountered when the drugs are administered systemically. Preliminary results from our laboratory have demonstrated the potential of our system to prevent cell death in a brain injury model. In this proposal, we will use a carrier to transport NGF, BDNF, and IGF-1 to specific sites within the brain as treatment for injured or degenerating neurons. This work is a model for a more general effort to design a system for site-specific delivery for a number of drugs and molecules within the brain. We have completed a pilot effort demonstrating improved cell survival with NGF treatment. In this Phase I of a Fast Track proposal we wilt obtain dose levels of drug to specific sites within the brain, establish the biologic activity of our unique compounds, and determine that we are able to reach the specific sites targeted for drug delivery.
