Cochlear Implant Gets an Upgrade with Gene Therapy This is a video of 3-D confocal imaging showing the cells secreting the neurotrophin (cyan) and the regenerated cochlear nerve (purple). Regenerated Auditory Nerves This shows regenerated auditory nerves, after gene therapy. This image relates to a paper that appeared in the Apr. 23, 2014, issue of Science Translational Medicine, published by AAAS. The paper, by Dr. J.L. Pinyon at the University of New South Wales in Sydney, NSW, Australia, and colleagues was titled, 'Close-Field Electroporation Gene Delivery Using the Cochlear Implant Electrode Array Enhances the Bionic Ear.' - Regrown nerves boost bionic ears Gene therapy aids performance of cochlear impants in guinea pigs. Nature 23 April 2014 doi:10.1038/nature.2014.15082 http://www.nature.com/news/regrown-nerves-boost-bionic-ears-1.15082 - Hearing quality restored with bionic ear technology used for gene therapy Existing cochlear technology used in a new way to re-grow auditory nerves http://www.eurekalert.org/pub_releases/2014-04/uons-hqr041714.php References 1. Pinyon, J. L. et al. Sci. Transl. Med. 6, 233ra54 (2014). Close-Field Electroporation Gene Delivery Using the Cochlear Implant Electrode Array Enhances the Bionic Ear Sci Transl Med 23 April 2014: Vol. 6, Issue 233, p. 233ra54 Sci. Transl. Med. DOI: 10.1126/scitranslmed.3008177 http://stm.sciencemag.org/content/6/233/233ra54 Abstract The cochlear implant is the most successful bionic prosthesis and has transformed the lives of people with profound hearing loss. However, the performance of the "bionic ear" is still largely constrained by the neural interface itself. Current spread inherent to broad monopolar stimulation of the spiral ganglion neuron somata obviates the intrinsic tonotopic mapping of the cochlear nerve. We show in the guinea pig that neurotrophin gene therapy integrated into the cochlear implant improves its performance by stimulating spiral ganglion neurite regeneration. We used the cochlear implant electrode array for novel "close-field" electroporation to transduce mesenchymal cells lining the cochlear perilymphatic canals with a naked complementary DNA gene construct driving expression of brain-derived neurotrophic factor (BDNF) and a green fluorescent protein (GFP) reporter. The focusing of electric fields by particular cochlear implant electrode configurations led to surprisingly efficient gene delivery to adjacent mesenchymal cells. The resulting BDNF expression stimulated regeneration of spiral ganglion neurites, which had atrophied 2 weeks after ototoxic treatment, in a bilateral sensorineural deafness model. In this model, delivery of a control GFP-only vector failed to restore neuron structure, with atrophied neurons indistinguishable from unimplanted cochleae. With BDNF therapy, the regenerated spiral ganglion neurites extended close to the cochlear implant electrodes, with localized ectopic branching. This neural remodeling enabled bipolar stimulation via the cochlear implant array, with low stimulus thresholds and expanded dynamic range of the cochlear nerve, determined via electrically evoked auditory brainstem responses. This development may broadly improve neural interfaces and extend molecular medicine applications.

• published: 01 May 2014
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