Date of Award
MCh by research (Master of Surgery by research)
Dr Justin Tan
Prof Frank Caruso
Prof Robert K. Shepherd
Hearing Loss; Nanoparticles
There are approximately 688,000 adults in the UK with severe to profound sensorineural hearing loss. While many people who suffer from hearing loss benefit from the use of a conventional hearing aid, these devices are not effective in patients with profound sensorineural hearing loss. Spiral ganglion neurons (SGNs) are the target cells of the cochlear implant, a neural prosthesis designed to provide important auditory cues to profoundly deaf patients. The ongoing degeneration of SGNs that occurs following sensorineural hearing loss is therefore considered a limiting factor in cochlear implant efficacy. Exogenous application of neurotrophic factors prevents SGN degeneration and can enhance neurite outgrowth. Both the quantity and the quality of surviving SGNs appear to be important for the success of the cochlear implant. The addition of BDNF to the cochlear fluids can prevent degeneration of SGNs after sensory hair cells are lost in adult rodent cochleae. This neurotrophin has to be continuously delivered to maintain neuronal survival as they are rapidly cleared by the body's physiological mechanism. Current available methods of neurotrophin application are limited to delivery over a period of less than one month, and carry risks of wound infection and viral inoculation. Alternative methods of delivery are needed. We developed a biodegradable and biocompatible polyglutarnic acid particle which along with glycosaminglycan heparin, successfully sequestered BDNF. This BDNF was shown to be released in a biologically active form over a period of 70 days. Its biological activity was confirmed using the neuroblastoma cell line SHSY5Y. These particles were then successfully inserted into a deafened rat cochlea and improved SGN survival. This work has shown that the PGA-heparin particles are potential carriers for BDNF, for clinical application in an effort to improve patient outcome with profound sensorineural hearing loss.
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Glynn FJ. A novel therapeutic approach encapsulating brain-derived neurotrophic factor in nanoparticles for treating sensorineural hearing loss. [MCh Thesis]. Dublin: Royal College of Surgeons in Ireland; 2010.