Professor Gary Housley is the Medical Lead of the Bionics and Bio-robotics pillar. Professor Housley has spent decades exploring the neural development of the auditory senses and brain injury and repair processes. The Bionic array Directed Gene Electrotransfer (BaDGE®) is now a flagship project for Tyree IHealthE.
What fascinates you about hearing?
People don’t realise it, but we only have 20,000 neurones in the ear. It’s not a lot. And they don’t regenerate. They are created in the first trimester, as a baby, and then they’ve got to last 100 years. About fifteen neurones go to each of the inner hair cells, where they form single synaptic puncta, like the finest little touch that you could imagine. So how do those neurones know that they’ve got to go to that one cell and then make that contact - and then that’s it for life? And that’s the challenge, holding on to those synapses across a lifetime.
How did your work collaboration with Cochlear get started? When I first came to UNSW about 15 years ago, I’d been looking at the neural development of the cochlea. And the people at UNSW Knowledge Exchange set me up in a meeting with the Chief Scientist of Cochlear, Jim Patrick, and I showed him my nice images of some of the proteins that are important for controlling nerve growth in the cochlea and determining why some nerve fibres target particular cells - and I can still remember Jim saying, “Gary, look, this is fantastic fundamental science, but we make cochlear implants so people can hear better. How can we find some common ground here to improve the engineering of cochlear implants?” And so that was interesting because that was a conversation I hadn’t had before - between industry, which is focussed on a challenge, and biomedical science, which had the tools.
You developed a method of bionic gene transfer therapy to regrow nerve fibres in the ear, using a very low-level electrical pulse. How has your relationship with Tyree IHealthE enhanced that work? Well, the next challenge was how to get this into clinical trials. And that involved Cochlear coming on as an industry partner to make an implant that could have a tube inside it to deliver the DNA solution, and which would use the wiring that we had optimised to create this electrical field for steering the DNA. But we were a bit puzzled as to why it was working so well, why we were getting good gene transfer with just a very, very small charge. Normally, if you were using two separate electrodes in the tissue, it would take damaging amounts of electricity to do it. Why was this so efficient? And that’s where the collaboration with Professor Nigel Lovell and the engineers came in. With their help, we learned that we were creating an electric lens, and that if you changed the configuration of the electrodes in the array you could control the field of delivery in a way that gene delivery has never been controlled before. And that’s why this project has worked – because of the skills that the different members of the team bring to the party. That’s the cross-disciplinary mix that makes all the difference here. Tyree IHealthE has established an ideal ecosystem across biomedical engineering and medical molecular engineering and neuroscience for refinement of the BaDGE platform and translation to promising gene therapy applications.
What is BaDGE?
The underlying knowledge breakthrough of the Bionic array Directed Gene Electrotransfer or BaDGE® project began with Professor Gary Housley’s work on the neural development of the cochlea. He studied the receptors that played a crucial role in establishing and maintaining synaptic connections between the sensory hair cells and the auditory neurons. From there grew an interest in developing the tools that would help control the expression of the genes responsible for those receptors.Years of development and broad collaboration has led to the creation of a first-in-kind gene electrotransfer device which creates a focused electric field to precisely steer naked DNA to target cells. This BaDGE device uses extremely low-intensity electric pulses to deliver DNA encoding genes for factors that stimulate rapid nerve repair. BaDGE is now in clinical trial to improve the hearing of patients receiving cochlear implants, where the resulting regrowth of the auditory nerve closes the gap with the cochlear implant array to improve hearing outcomes.
Compounding successes have encouraged the team to look into other applications for BaDGE. Early investigations suggest promising opportunities in the treatment of epilepsy and Parkinson’s Disease. The technology is also proving effective for targeted delivery of genes to the eye, establishing the foundation for new non-viral DNA and RNA therapeutics to treat loss of vision.
At Tyree IHealthE, we are working to migrate this technology into a broad electro-therapeutic platform. Now that we understand and can control the electric field focusing process, we’ve actually been able to modify the BaDGE® technology for safe delivery of a DNA or RNA solution into the brain. And with National Health and Medical Research Council (NHMRC) funding, we’re collaborating with clinical scientists at the University of Tübingen in Germany to develop DNA molecules that will suppress the hyper-excitability of local neural circuits. So, the challenge is whether we can provide very precise expression of these therapeutic molecules to regulate neural circuit excitability of the brain, potentially to treat epilepsy.
Professor Gary Housley
Bionics and Bio-robotics Medical Lead
The BaDGE team members