Browsing by Author "Hume, Clifford"

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    Halting the progression of noise-induced hearing loss with gene therapy
    (2013) Richardson, Rachael; Atkinson, Patrick; Wise, Andrew; Flynn, Brianna; O'Leary, Stephen; Hume, Clifford; Shepherd, Robert
    Progressive hearing loss is often ignored until there is significant loss of cochlear hair cells (HCs) and spiral ganglion neurons (SGNs). It usually begins as a mild high-frequency threshold shift which worsens and also spreads to the lower frequencies. Our previous research indicated that gene therapy is effective for long-term preservation of SGNs when administered shortly after ototoxic hearing loss, but has greater potential to protect residual HCs and SGNs after the onset of progressive hearing loss and even to restore hearing.
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    Neurotrophin gene therapy for sustained neural preservation after deafness
    (PLOS, 2012-12-17) Atkinson, Patrick; Wise, Andrew; Flynn, Brianna; Nayagam, Bryony; Hume, Clifford; O'Leary, Stephen; Shepherd, Robert; Richardson, Rachael
    The cochlear implant provides auditory cues to profoundly deaf patients by electrically stimulating the residual spiral ganglion neurons. These neurons, however, undergo progressive degeneration after hearing loss, marked initially by peripheral fibre retraction and ultimately culminating in cell death. This research aims to use gene therapy techniques to both hold and reverse this degeneration by providing a sustained and localised source of neurotrophins to the deafened cochlea. Adenoviral vectors containing green fluorescent protein, with or without neurotrophin-3 and brain derived neurotrophic factor, were injected into the lower basal turn of scala media of guinea pigs ototoxically deafened one week prior to intervention. This single injection resulted in localised and sustained gene expression, principally in the supporting cells within the organ of Corti. Guinea pigs treated with adenoviral neurotrophin-gene therapy had greater neuronal survival compared to contralateral non-treated cochleae when examined at 7 and 11 weeks post injection. Moreover; there was evidence of directed peripheral fibre regrowth towards cells expressing neurotrophin genes after both treatment periods. These data suggest that neurotrophin-gene therapy can provide sustained protection of spiral ganglion neurons and peripheral fibres after hearing loss.