Grants We Funded

Abstract
In Obsterical Brachial Plexus Palsy, nerves are stretched and sometimes ruptured during delivery leaving more than 25% of infants with permanent paralysis, numbness, or chronic pain for the duration of their lives. An overlooked component of disability following neonatal nerve injury is the death of central motor and sensory neurons crucial for repair and regeneration. Rat models have shown that over 70% of motor neurons and 60% of sensory neurons die following neonatal nerve injury. Similar findings have been observed in higher mammals, including monkeys, and even a human case. Axons are incapable of regenerating without neuronal guidance, and improving neuronal survival may increase axonal regeneration and recovery. Presently, acute management of neonatal nerve injury is exclusively surgical. Pharmacologic protection against neuronal cell death would represent a major paradigm shift.
Studies in our laboratory have demonstrated that P7C3 protects neurons following peripheral nerve injury and increasing neuron survival improves functional recovery. However, the mechanism of P7C3 remains unknown and it is not yet approved for clinical use. The anti-oxidants N-acetyl cysteine (NAC) and acetyl-L-carnitine (ALC) have a long history of safe clinical use and have demonstrated neuronal protection in adult models of nerve injury. NAC and ALC have not been investigated in neonatal peripheral nerve injuries where neuron death is most profound. NAC and ALC, if shown to be effective, are more realistic candidates for clinical translation because of their documented history of safety in pediatric populations. This proposed pilot research grant will begin investigation into how NAC and ALC effect neuron survival, regeneration, and recovery after neonatal nerve injury. If positive, this research will provide a novel mechanism for protecting the nervous system after peripheral nerve injury, which could realistically be translated to a clinical setting to greatly improve patient outcomes in conjunction with conventional surgical methods.

Biography
I completed my undergraduate degree at McMaster University and medical school at the University of Ottawa, where I was awarded the Gold Medal in recognition of achieving the highest academic standing in my class. In 2011, I was accepted into the Plastic Surgery Program at the University of Toronto and subsequently into the prestigious Royal College of Physicians and Surgeons of Canada Clinician-Investigator Program, which provides additional funding to pursue graduate research full-time. My PhD is under the supervision of Dr. Gregory H. Borschel at the Hospital for Sick Children. My research focuses on corneal neurotization, which is a novel surgical solution to restore vision in patients with corneal anesthesia. I am involved in both the clinical outcomes assessment and the development of an animal model of corneal neurotization in the laboratory. This model will further our understanding of how the corneal innervation influences the corneal epithelium and will provide a paradigm with which innovations to improve the outcomes of corneal neurotization can be investigated. My laboratory research compliments my clinical research aims, which are to definitively document nerve regrowth following neurotization using in-vivo corneal microscopy and to investigate how innervation affects the gene and protein expression in the corneal epithelium.