INNOVATION ARTICLES THE IDEA SUBMISSION PORTAL FROM MEDTRONIC


Professor Gary Housley

Cochlear Implant Delivered Gene Therapy Regrows Auditory Nerves

Professor Gary Housley

Marie Gethins
October 2015

In 1976, French Professor Claude-Henri Chouard performed the first cochlear surgical implant in Paris. Less than 40 years later, by the end of 2012, more than 324,000 patients have benefited from the devices worldwide. Unlike hearing aids that amplify sound, internal cochlear implants bypass damaged portions of the ear and directly stimulate auditory nerves. The technology has continued to advance over the past three decades, but current research in cochlear implant delivered gene therapy shows exciting potential to actually regrow auditory nerves. This could provide patients with a greater dynamic range of sound.

Surgically implanted electronic devices, cochlear implants have both external and internal components. The internal portion consists of a transmitter which is implanted into the mastoid bone behind the ear with electrodes inserted into the cochlea. A microphone and speech processor are attached externally and send sounds as electrical signals to the electrodes, which stimulate the auditory nerves and send signals to the brain perceived as sound.

Several gene therapeutic approaches are under investigation to address hearing impairment including adenovirus and adeno-associated virus based therapies. Another stream of research is exploring the use of gene therapy to enhance the performance of cochlear implants. Naturally occurring proteins, or neurotrophins, when delivered to the cochlea of the ear and stimulated, can regenerate auditory nerve endings. However in addition to electrical stimulation hurdles, gene delivery also faces a physical challenge with four tight spirals in the delicate human ear.

An Australian study, largely funded by the government National Health and Medical Research Council and the Garnett Passe and Rodney Williams Memorial Foundation is working on possible solutions to these barriers. Principal Investigator, Professor Gary Housley of the University of New South Wales (UNSW), Sydney, Australia described the idea behind the highly localised gene therapy used in their pre-clinical trial. “The concept was to deliver a neutrotrophin product in the cochlea and use the implant as the current source,” he said.


IT DOESN’T TAKE THAT MANY CELLS TO HAVE A THERAPEUTIC EFFECT.


In a guinea pig model, after the device was installed, the research team used an electrode array to deliver brief, intense pulses to temporarily open the cell membrane. This “electroporation” enables genetic solution material to pass into the mesenchymal cells that line the scala tympani. Inside the cell nuclei, the genetic material produce brain-derived neurotrophic factor, leading to restoration of hearing. Housley reports, “It doesn’t take that many cells to have a therapeutic effect.” In the guinea pig trial, expression fell off after a few months with nerve fibres beginning to atrophy once again. Housley says this was due to lack of use, which is unlikely to be an issue in human cases. He also notes that due to size limitations, only the first spiral of guinea pig cochlear could be accessed and there is the possibility to go further in human trials.

The next phase of the Australian research is migration to a cat model, as physically the cat ear is closer to the human ear in spiral compression. Plans are for a human safety and efficiency study late 2016 with approximately 15 adult participants.

On the innovation behind the therapeutic approach, Housley stresses the importance of collaboration for success. In addition to UNSW researchers, experts from Macquarie University, the University of Melbourne, the Royal Prince Albert Hospital, and Cochlear Limited are involved in the project. He highlights that as well as medical and technical device expertise, patient support is essential as training and learning to use the cochlear implant are vital elements of the treatment. Currently patients with cochlear implants can become adept at understanding most speech, but there are pitch limitations. This can affect not only their enjoyment of music, but also there are significant tonal variations in general speech and communication can be significantly affected by reduced tonal range for some dialects, including many Asian languages.

In a July 2015 Science Translational Medicine review article, Professor Tobias Moser of the Georg-August-Universität Göttingen, Germany predicted that: “pioneering gene therapy studies [including the cochlear implant delivery] provide hope that restoration of hearing will become available for select forms of deafness within the next decade or so.” While cautioning that the Australian cochlear implant delivery gene therapy studies are in pre-clinical phases, Professor Gary Housley is equally optimistic that the research could achieve important gains in addressing hearing loss over a relatively short time.


References

1

Interview with Professor Gary Housley, July 2015

2

The early days of the multi-channel cochlear implant: efforts and achievement in France. (2014) Available here: http://www.ncbi.nlm.nih.gov/pubmed/254991

3

Cochlear implants (2014) Available here: http://www.nidcd.nih.gov/health/hearing/pages/coch.aspx

4

Gene therapy for deafness: How close are we? (2015) Available here: http://stm.sciencemag.org/content/7/295/295fs28

5

Close-Field Electroporation Gene Delivery Using the Cochlear Implant Electrode Array Enhances the Bionic Ear (2014) Available here: http://stm.sciencemag.org/content/6/233/233ra54