Neurotrophin gene therapy for sustained neural preservation after deafness

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dc.contributor.authorAtkinson, Patrick
dc.contributor.authorWise, Andrew
dc.contributor.authorFlynn, Brianna
dc.contributor.authorNayagam, Bryony
dc.contributor.authorHume, Clifford
dc.contributor.authorO'Leary, Stephen
dc.contributor.authorShepherd, Robert
dc.contributor.authorRichardson, Rachael
dc.date.accessioned2013-05-08T05:51:22Z
dc.date.available2013-05-08T05:51:22Z
dc.date.issued2012-12-17
dc.description.abstractThe 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.en_US
dc.description.sponsorshipAction on Hearing Loss (http://www.actiononhearingloss.org.uk/, The Garnett Passe and Rodney Williams Memorial Foundation, The National Institutes of Health (http://www.nih.gov/)(NIDCD HHS-N-263-2007-00053-c, NIDCD DC-006437, NIDCD P30 DC-04661, NICHHD P30 HD-02774), The University Of Melbourne Department Of Otolaryngology (http://www.unimelb.edu.au/), The Royal Victorian Eye and Ear Hospital (http://www.eyeandear.org.au/), The Hearing Regeneration Initiative (http://www.hearingregeneration.com/), The Veterans’ Hospital Administration, The State Government of Victoria’s Operational Infrastructure Program (http://www.business.vic.gov.au/).en_US
dc.identifier.citationAtkinson, P., Wise, A., Flynn, B. O., Nayagam, B. A., Hume, C., O'Leary, S., Shepherd, R., & Richardson, R. (2012). Neurotrophin gene therapy for sustained neural preservation after deafness. PLOS One, 7(12), e52338.en_US
dc.identifier.issn1932-6203
dc.identifier.urihttp://repository.bionicsinstitute.org:8080/handle/123456789/26
dc.language.isoenen_US
dc.publisherPLOSen_US
dc.subjectBrain-Derived Neurotrophic Factor - therapeutic useen_US
dc.subjectCochlear Implantationen_US
dc.subjectCochlear Nerve - drug effectsen_US
dc.subjectCochlear Nerve - pathologyen_US
dc.subjectDeafness - drug therapyen_US
dc.subjectDeafness - pathologyen_US
dc.subjectNeurons - drug effectsen_US
dc.subjectNeurons - pathologyen_US
dc.subjectAdenoviridae - geneticsen_US
dc.subjectBrain-Derived Neurotrophic Factor - geneticsen_US
dc.subjectCell Survivalen_US
dc.subjectGene Expressionen_US
dc.subjectGenetic Therapy - methodsen_US
dc.subjectGenetic Vectorsen_US
dc.subjectNeurotrophin 3 - geneticsen_US
dc.subjectNeurotrophin 3 - therapeutic useen_US
dc.subjectRecombinant Proteins - therapeutic useen_US
dc.subjectRecombinant Proteins - geneticsen_US
dc.subjectSpiral Ganglion - physiopathologyen_US
dc.titleNeurotrophin gene therapy for sustained neural preservation after deafnessen_US
dc.typeArticleen_US
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