Cochlea implant delivers gene therapy

Existing cochlear implant technology has been used in a new technique to deliver genes to cells of the inner ear and stimulate nerve regrowth.

The research holds promise for enhancing the performance of cochlear implants as well as treating a range of neurological disorders, such as Parkinson’s disease, and conditions such as depression.

“People with cochlear implants do well with understanding speech, but their perception of pitch can be poor, so they often miss out on the joy of music,” said Professor Gary Housley, Director of the Translational Neuroscience Facility at UNSW Medicine where the research was conducted.

“Ultimately, we hope that after further research, people who depend on cochlear implant devices will be able to enjoy a broader dynamic and tonal range of sound, which is particularly important for our sense of the auditory world around us and for music appreciation,” he added.

It has long been established that the auditory nerve endings regenerate if neurotrophins like brain-derived neurotrophic factor (BDNF) - a naturally occurring family of proteins crucial for the development, function and survival of neurons - are delivered to the auditory portion of the inner ear, the cochlea. The auditory nerve fibres reside in the cochlea from which they transfer sound waves directly to the brain.

Until now, research into the localised delivery of neurotrophins to the cochlea has stalled because a safe way of using drug delivery or viral-based gene therapy has not been attained.

Professor Housley and his team at UNSW developed a way of delivering ‘close-field’ electroporation gene therapy from the cochlear implant to deliver DNA to the cells close to the array of implanted electrodes. The technique uses a series of brief but intense electric pulses to increase the permeability of the cell membrane. In this way, complementary DNA (cDNA) for BDNF was transferred into the mesenchymal cells lining the cochlea of guinea pigs. These cells then produced BDNF, which dropped off after a couple of months.

“No-one had tried to use the cochlear implant itself for gene therapy,” said Professor Housley.

“With our technique, the cochlear implant can be very effective for this.”

The cochlear implants are “surprisingly efficient” at localised gene therapy in the animal model, when a few electric pulses are administered during the implant procedure.

“We think it’s possible that in the future this gene delivery would only add a few minutes to the implant procedure,” said Jeremy Pinyon, whose PhD is based on this work. “The surgeon who installs the device would inject the DNA solution into the cochlea and then fire electrical impulses to trigger the DNA transfer once the implant is inserted.”

Integration of this technology into other ‘bionic’ devices such as electrode arrays used in deep brain stimulation (for the treatment of Parkinson’s disease and depression, for example) could also provide the opportunity for safe, directed gene therapy of complex neurological disorders.

“Our work has implications far beyond hearing disorders,” said Associate Professor Matthias Klugmann, from the UNSW Translational Neuroscience Facility research team. “Gene therapy has been suggested as a treatment concept even for devastating neurological conditions and our technology provides a novel platform for safe and efficient gene transfer into tissues as delicate as the brain.”

The research has been five years in development and has the support of Cochlear Ltd through an Australian Research Council Linkage Project grant.

The research has been published in Science Translational Medicine.

Figure caption: Comparison of the cochlear nerve after neurotrophin gene therapy (top) versus the untreated cochlea from the same animal (bottom). Image courtesy of UNSW Australia Translational Neuroscience Facility, J Pinyon and G Housley.