Name: Professor Gary Housley
Position/s: Scientia Professor Gary Housley, Director, Translational Neuroscience Facility, Chair of Physiology, School of Medical Sciences.
Theme and CAG position:
Sub theme leader for Brain Sciences and Translational Neuroscience
Research program: Team leader of the sensori-motor physiology & therapeutics (SMPT) research group in the Department of Physiology & Translational Neuroscience Facility.
The team’s research program engages molecular neuroscience and biomedical engineering in applications spanning two translational themes:
Theme 1: Hearing Therapeutics and Diagnostics - Studies directed to treatment and prevention of hearing loss:
(A) Cochlear implant neurotrophin gene therapy clinical trial; a first-in-human phase I/II non-randomized, controlled trial, evaluating the safety and efficacy of neurotrophin gene therapy delivered during cochlear implant surgery (www.cingt.info). The study utilises a proprietary DNA electrotransfer platform technology developed at UNSW in the labs of Gary Housley and Sci. Prof. Nigel Lovell (Biomed Eng), the BaDGE® ‘Bionic array Directed Gene Electrotransfer’ medical device patent families). Through partnership with Cochlear Ltd, this is a new medical device and “drug” combination for directed delivery of a novel naked DNA therapeutic molecule encoding neurotrophins during cochlear implant surgery to regenerate of the cochlear nerve and improve hearing performance with the ‘Bionic Ear’. This involves three other Australian Universities (U. Sydney, U. Melbourne, Macquarie University), the Sydney Cochlear Implant Centre, Cochlear Ltd and international collaborations. Over 30 collaborators are currently contributing to this NHMRC-funded study. The first two gene therapy subjects underwent the procedure in Q2 – Q4 this year. The trial is anticipated to run to December 2022, following a decade-long pre-clinical development of the cochlear - BaDGE® auditory nerve repair application. BaDGE® is a derivative to pulsed electric field ‘electroporation’ technology that is highly efficient at localized electrotransfer of ‘naked’ DNA encoding therapeutic proteins to targeted tissues. BaDGE® is currently under development for a range of applications.
(B) Clinical study of ‘Noise-induced hearing adaptation’ (NIHA) to establish a prognostic hearing test of vulnerability to hearing loss. An audiology-based study incorporating development of innovative hearing assessment procedures to enable the study of NIHA. This study will assess the response of the ear to a ‘noise stress test’ across populations, ethnicities, age-groups and work environments, reflecting ‘purinergic hearing adaptation’ as a biomarker for resistance to hearing loss (UNSW patent). The study seeks to create a first-in-class prognostic hearing test to identify individuals at-risk for hearing loss (viz. those with a weak NIHA profile). The study involves collaborating centres of audiology and hearing genetics across seven centres in five countries (Australia, New Zealand, USA, and China). This is supported by industry partnership with a leading hearing diagnostics company and funded by an NHMRC Ideas grant (2020 – 2024) that supports pre-clinical studies utilizing transgenic mouse models to probe the underlying purinergic signaling connectome.
(C) Mechanotransducer gene augmentation to confer auditory neurons with sensitivity to sound: Sensori-neural hearing loss (disruption of the cochlear sensory hair cell – auditory neuron connectivity) is the principal element of noise- and age-related deafness, which is the most pervasive and impactful sensory disability in Society. In this project, we utilize a biomimetic strategy that seeks to confer direct acoustic sensitivity to mammalian auditory neurons in a manner evident in lower vertebrate models. This is an NHMRC-funded ‘Ideas’ project that extends the utility of the cochlear - BaDGE® technology, by delivering plasmid DNAs with expression cassettes encoding mechanotransducer ion channels to cochlear auditory neurons alongside neurotrophin-gene augmentation for auditory nerve fibre regeneration; aiming to restore sound sensation in the absence of sensory hair cells.
Theme 2: Brain Repair Therapeutics
This research theme is centered on industry partnerships to develop novel neuroprotection drugs and DNA therapies for acquired brain injury, and focal CNS disorders:
(D) Developing a drug to treat acquired brain injury: Initiated by a novel neuroprotection target based on identification of the contribution of the TRPC ion channel – metabotropic glutamate receptor signalling complex to calcium overload in brain injury models (UNSW patent), this program is an industry collaboration which has built to a rational drug development program to create a first-in-class small molecule drug to reduce mortality and morbidity with stroke and traumatic brain injury (TBI). This UNSW research collaboration contributed to the establishment of a new Biotech startup, Nyrada Inc. in January 2019 (www.nyrada.com; ASX listed Jan. 2020), with Gary Housley serving as Chair of the scientific advisory board (COI declaration). The collaboration established models in the UNSW Translational Neuroscience Facility for pre-clinical focal ischaemic brain injury (photothrombotic infarcts), as a highly reproducible brain injury model for evaluating drug efficacy. This collaboration includes industry - university interchange.
(E) Focal epilepsy: a ‘Brain-BaDGE®’ - DNA gene augmentation application: This project is directed to utilizing BaDGE® technology for the safe targeted delivery of naked DNA to the brain to control focal epilepsy. The project engages the UNSW BaDGE® development team with overseas industry partners and international university collaborations to develop a novel ‘naked’ DNA therapeutic for targeted neuromodulation of hyperexcitability.
As sub-theme leader for brain sciences and translational neuroscience, what are you hoping to achieve?
To promote an environment of research opportunity for innovation through multi-disciplinary collaboration, mentoring and networking (internal and external). In parallel, we must promote education around the opportunity, vision, and potential hazards which the Neurosciences trajectory portends.
How has the Neuroscience, Mental Health and Addiction Theme and CAG facilitated new opportunities in research and/or collaboration in the Brain Sciences and Translational Neuroscience subtheme? What are some of the highlights to date?
The key success has been the take-up of seed funding initiatives that have seen innovative projects supported, creating new science from the bench up and bridging to clinicians who delineate the translational pathway. In the past two years, the NMHA theme has provided seed funding stimulus opportunities to the sub-theme, and 12 projects have been funded. Feedback from the seed funded teams has validated the hugely strategic value of practical promotion of the latent capacity in the current unprecedented challenges of the present time. Some of the funded projects have evolved into successful category 1 grant applications/projects. Complementing this, we have had the benefit from engagement with leaders in industry and philanthropy who have contributed to the critical aspect of translational neuroscience, which is the partnership between the community, research teams and the biotech structures which carry the innovation through to new standards of care, new biomedical technologies and ultimately a healthier and productive Society.
What do you see as the emerging areas of research priorities in Brain Sciences and Translational Neuroscience?
Translational neuroscience is at the nexus of scientific discovery and clinical enablement. This is central to the broader need for conversations between the community, clinicians and biomedical researchers, to understand and prioritize research for impact in areas of pressing unmet need. Hearing loss and acquired brain injury are at the forefront of health burden in this context, and the life-long morbidity experienced by victims of these conditions sits alongside profound impacts on family and community. In the broader sense, Brain Sciences and Translational Neuroscience are at nub of what could be argued as the greatest challenge human Society has experience to date – namely the biotech revolution which is making information access and processing central to the lives of everyone in our communities. This is reflected in the massive corporate investment in the mind-machine interface (e.g. https://neuralink.com/); an all pervasive interface spanning from smart devices now effective / seemingly indispensable in the hands of babies, to first prototypes of implanted brain - neuron interfaces for mind control of devices and communication. This revolution poses massive challenges to Society to ‘cope’ with the inevitable disruptions around equity, diversity and ethics, and competitiveness from the level of individual to nations. It is imperative that we have the knowledge, training and judgement to contribute responsibly to this truly transformative scientific / industrial frontier.