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Regrowth of auditory nerve fibres within two weeks of delivery of naked DNA encoding BDNF to the cochlea. The DNA was taken up by the cells lining the cochlear fluid compartment when electrical pulses where delivered to a cochlear implant array reconfigured to produce a highly focused electric field in a deafened guinea pig model. These cells read the DNA and produced a localized concentration of the neurotrophic factor, which provided a directional stimulus for regrowth of the nerve fibres which would ‘close the neural gap’ with the cochlear implant array. The image by Jeremy Pinyon (after Sci. Trans. Med. 2014), out of the Translational Neuroscience Facility, School of Medical Sciences at UNSW Sydney, specifically immunolabels the spiral ganglion neurons in a cryosection, with the cell bodies evident to the right and the regrowth of the peripheral neurites outlined by arrowheads
A first-in-human clinical trial seeks to improve hearing outcomes for patients receiving a cochlear implant using gene augmentation therapy. Fifteen patients will be recruited into the Treatment Group from early 2019 at the Royal Prince Alfred Hospital in Sydney, in a collaboration involving clinicians and researchers across five institutions and industry partner Cochlear Ltd. The gene therapy will utilize the cochlear implant electrode array to provide electrical transfer of naked DNA encoding factors (neurotrophins) that promote cochlear nerve repair to cells lining the fluid chamber of the cochlea. In pre-clinical animal studies, when the neurotrophins are produced at this site, the cochlear nerve fibres grow out towards the cochlear implant electrodes, thereby “closing the neural gap” and improving the interface between the auditory prosthesis and the cochlear nerve. The funding from this grant will enable a progressive comparison of the improvement in hearing over time from the treatment group and a matched Reference Group, based on objective and subjective measures obtained during 9 visits to the Sydney Cochlear Implant Centre site in the 12 months following surgery.
Professor Housley and Associate Professor Birman wish to acknowledge their co-investigators on this project: Dr. Waikong Lai, Dr. Jeremy Pinyon, and Prof. David McAlpine.