Cochlear implants have given thousands of people around the world the ability to hear, a remarkable achievement, but one that needs improvement to provide long term, high-fidelity hearing. This is because the tips of the acoustic nerve bundles that the implants stimulate become sickly and ineffective at absorbing the electrical signals. The implants end up having to stimulate the nerves with a broader signal that reduces the overall sound quality. Researchers at University of New South Wales, Australia wanted to investigate whether gene therapy can be an effective tool to maintain the health of auditory nerves and came up with a convenient way of introducing genes just where needed.
Viruses are the most common vehicle for getting DNA into the interior of living cells because they’re experts at penetrating cellular membranes, but they carry the risk of causing new diseases. The researchers realized that since the auditory nerves being treated already have the cochlear implant ready to stimulate them, they can use it to electrically open up pores within nerve cells to let the DNA in on its own. They used deaf guinea pigs and used the technique to inject genes that code for neurotrophin, a protein that stimulates the growth of nerves. Post treatment, the researchers discovered that the auditor nerve regenerated and naturally grew toward the cochlea, improving the pigs’ hearing.
From the study abstract in Science Translational Medicine:
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.
Study in Science Translational Medicine: Close-Field Electroporation Gene Delivery Using the Cochlear Implant Electrode Array Enhances the Bionic Ear…