Neurotrophin gene therapy for sustained neural preservation after deafness.

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 de...

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Main Authors: Patrick J Atkinson, Andrew K Wise, Brianna O Flynn, Bryony A Nayagam, Clifford R Hume, Stephen J O'Leary, Robert K Shepherd, Rachael T Richardson
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0052338&type=printable
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author Patrick J Atkinson
Andrew K Wise
Brianna O Flynn
Bryony A Nayagam
Clifford R Hume
Stephen J O'Leary
Robert K Shepherd
Rachael T Richardson
author_facet Patrick J Atkinson
Andrew K Wise
Brianna O Flynn
Bryony A Nayagam
Clifford R Hume
Stephen J O'Leary
Robert K Shepherd
Rachael T Richardson
author_sort Patrick J Atkinson
collection DOAJ
description 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.
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spelling doaj-art-c6f87e92dea946a59d7d19dbbf4db9b22025-08-20T03:26:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01712e5233810.1371/journal.pone.0052338Neurotrophin gene therapy for sustained neural preservation after deafness.Patrick J AtkinsonAndrew K WiseBrianna O FlynnBryony A NayagamClifford R HumeStephen J O'LearyRobert K ShepherdRachael T RichardsonThe 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0052338&type=printable
spellingShingle Patrick J Atkinson
Andrew K Wise
Brianna O Flynn
Bryony A Nayagam
Clifford R Hume
Stephen J O'Leary
Robert K Shepherd
Rachael T Richardson
Neurotrophin gene therapy for sustained neural preservation after deafness.
PLoS ONE
title Neurotrophin gene therapy for sustained neural preservation after deafness.
title_full Neurotrophin gene therapy for sustained neural preservation after deafness.
title_fullStr Neurotrophin gene therapy for sustained neural preservation after deafness.
title_full_unstemmed Neurotrophin gene therapy for sustained neural preservation after deafness.
title_short Neurotrophin gene therapy for sustained neural preservation after deafness.
title_sort neurotrophin gene therapy for sustained neural preservation after deafness
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0052338&type=printable
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