Efficient Delivery of Optimized Painless Nerve Growth Factors to the Central Nervous System to Treat Spinal Cord Injuries - Project Summary The incidence rate for traumatic spinal cord injuries (SCIs) in the United States is estimated to be 54 cases per million people or 17,900 new cases each year. SCIs have devastating consequences for the physical, emotional, social, and vocational well-being of patients. The direct cost for the care of SCI patients is staggering at $1.1-5.2 million per patient over their lifespan. Compared to civilian SCIs, SCIs in battlefield shows increased severity and poorer neurological recovery. Delayed access to surgical spinal decompression and stabilization after a SCI is the main cause for poor outcome. Therefore, treatments that can be used through systematic injection, when surgical intervention is delayed, in order to limit the secondary injury and promote regeneration is of urgent need. Advances in medical care of SCIs have taken place in the past two decades, however, effective treatments are still limited. Pharmacological strategies, directly working on endogenous neurons, is highly effective due to their neuroprotective and neuroregenerative capabilities. Nerve growth factor (NGF) is the first discovered neurotrophin that plays a major role in the neural development of the central nervous system (CNS). However, NGF is not currently available to patients due to its 1) poor penetration into the CNS, 2) limited duration of bioavailability, and 3) enhanced nociceptor response. To address these issues and provide an effective solution for SCI treatment, we propose to utilize a double- encapsulation system to achieve effective delivery and controlled-release of painless NGF variant (NGFp), which can preserve, protect, and regenerate the injured neurons to improve neurologic outcomes in spinal cord injuries while dissipating pain. Specifically, we are applying a novel nanotechnology platform named “nanocapsules” to effectively deliver NGFp into the spinal cord facilitated by choline transporters. Moreover, the double- encapsulation system can entrap NGF nanocapsules within double emulsions to precisely control the release kinetics of nanocapsules. Lastly, we will deliver NGFp, which has a reduced nociceptive response, but potent neurotrophic and neuroprotective capability compared to wild-type NGF. Success of this project will provide an effective treatment for SCI patients to improve neurologic outcomes and quality of life.
