Ectopic Olfactory Receptor Guided Facial Nerve Regeneration

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ABSTRACT Injury to the facial nerve leaves the patient with limited ability to communicate with facial expression leading to reduced quality of life, depression, suicide and social isolation. The facial nerve connects to specific muscles in the face to control movement, such as the eye blink or smiling. When the facial nerve is cut it tries to regrow and reconnect to the muscles of the face, but it lacks the proper signals to guide or steer it towards the correct original muscles that it previously innervated. This incorrect rewiring leads to painful eye closure when a person wants to smile and is termed synkinesis. There are no treatments available today that can prevent synkinesis. Attempts at facial nerve reconstruction require multiple risky surgeries and lengthy hospitalizations often with limited improvements. Therefore, the objective of this project is development of novel techniques to guide facial nerve reconnection to the facial muscles and ultimately to achieve normal facial expression. To restore the original topographic organization of the facial nerve, we will first examine the expression of proteins in facial motoneuron subnuclei. Once these proteins are identified, we will then test if these proteins can guide motoneurons in microdevices simulating facial nerve branching. Following this characterization, we will design nerve grafts that act as guides for regenerating axons that contain the ligands to activate these proteins and steer the nerves towards their correct muscle target. We expect that nerve grafts with topographically positioned ligands for guidance will substantially reduce synkinesis. We will study the efficacy of these designer nerve grafts in the rat. The rat facial nerve is a well-accepted model to study facial nerve regeneration in mammals. The rat facial nerve independently controls whisker movement and eye blinking, however after injury using high speed cameras, we can precisely quantify synkinesis or extent of simultaneous blinking and whisker motion. This breakthrough would translate to patients with improved facial nerve recovery, reduced depression, and social isolation facilitating reintegration into society. The results of this work could have a path to translation into human clinical trials, as we will adapt currently used nerve grafts to contain the guidance molecules we identify in this study. This novel technology could also be readily adapted to other peripheral nerve injuries.