Submission to the Parliamentary Inquiry into the Hearing Health and Wellbeing of

384-388 Albert Street, East Melbourne, 3002

Web: www.bionicsinstitute.org

My name is Professor Robert Shepherd and I am writing this submission as Director of The Bionics Institute of Australia.

The Bionics Institute is a not-for-profit, independent, medical research institute located in Melbourne dedicated to the research and development of devices that interface with the nervous system to create new treatments for serious medical conditions.

The (then) Bionic Ear Institute was established in 1984 by Professor Graeme Clark, leader of the team that created Australia’s first multi-channel cochlear implant (often referred to as the bionic ear) in the late 1970s. This bionic device was subsequently commercialised by Nucleus/Cochlear Ltd in the 1980s and has provided the gift of hearing to approximately 450,000 adults and children in over 120 countries world-wide. Professor Clark established the Institute to ensure that work continued to improve and build on this innovative technology within an independent, multi-disciplinary research environment.

To this day, hearing and deafness research, and ongoing improvement in the performance of the cochlear implant and other hearing devices, form a core research program within the Bionics Institute.

From this perspective, and with over 35 years personal experience in cochlear implant and hearing research, I write on behalf of the Bionics Institute to comment on the following two terms of reference of this parliamentary inquiry:

• Whether hearing health and wellbeing should be considered as the next National Health Priority for Australia • Developments in research into hearing loss, including: prevention, causes, treatment regimes, and potential new technologies

The economic and personal impact of hearing loss and ear disorders

In 2015, the World Health Organisation estimated that 360 million people world-wide had a disabling hearing loss [1]. The most recent comprehensive analysis of the impact of hearing loss in Australia was carried out in 2006 by Deloite Access Economics [2]. While this document is now a

Page | 1 decade out of date, it identified that hearing loss represents a real financial cost to Australia of $11.75 billion per annum or 1.4 percent of GDP. This report indicated that three in every four Australians aged over 70 years are affected by hearing loss, and predicted that by 2050 one in every four Australians would be impacted. With the ageing population economic and healthcare costs are only set to increase.

Economic costs are paralleled by impact on an individual’s quality of life. Hearing loss affects the most fundamental of our abilities: the capacity to interact using oral language with our fellow human beings. It is a particularly disabling condition because it affects the ability to communicate verbally, hear and respond to environmental danger signals, and engage aesthetically with music and other sounds. The combination of these factors means that hearing impairment can lead to disengagement with society and isolation. There is compelling evidence that hearing loss is linked to cognitive decline and dementia [e.g., 3]. There is also a strong link between untreated hearing loss and a range of negative emotions including sadness, anxiety, and feelings of insecurity, as well as depression [4, 5]. Hearing loss is also associated with a disengagement from the economy. In 2006, almost 160,000 people in Australia were not working because of a hearing impairment, costing an estimated $12 billion per year [2].

While prevalence rates for hearing loss increase with age, the impact of hearing loss and deafness in children has life-long consequences. Congenital deafness or hearing loss through injury or illness early in life can have a severe effect on quality of life, and can impair language development with a resulting impact on educational attainment, social skills, and future employment opportunities. Early access to hearing is crucial for the development of the brain networks that are involved in language perception and speech production. The introduction of newborn hearing screening – an Australian innovation – along with improved hearing aid technology has greatly improved language development in deaf children. Early intervention produces precious life-long social, educational, career and employment benefits. That is why infants as young as two months are receiving cochlear implants and hearing aids. However, although there is a large average benefit for earliest possible provision of hearing devices (made possible by newborn hearing screening), even those children with the earliest intervention show a wide range of language development. Some children respond and develop well with their hearing devices while others are left behind.

Considerations of the impact on Australia of hearing health become even more dramatic when other disorders of the ear are considered. I highlight just two examples here.

• Otitis media (middle ear infection) is a common illness in children and particularly prevalent in Indigenous Australians. A study in 2009 estimated that otitis media affected between ~ 992,000 - 2.4 million Australians and cost around $100 - $400 million [6]. Otitis media can lead to a temporary and mild hearing loss (due to the blocking of sounds through the middle ear) that is reversed once the infection is resolved with antibiotics. However, complications arise if the infection is untreated or poorly treated, with the extreme outcome being permanent hearing loss. Chronic and severe infections are much more prevalent in Indigenous children

Page | 2

than non-Indigenous children [6]. The recurring hearing impairment can impact speech and language development, and this in turn has life-long consequences for education, social engagement, and employment. • Tinnitus is an indication of damage to the inner ear that is often associated with hearing loss. It is the perception of sound (usually ringing or buzzing) in the absence of external sounds and affects approximately 18 percent of Australians at some point in life. About 1-3 percent of people suffer from debilitating chronic tinnitus which significantly decreases their quality of life. Tinnitus has been strongly correlated with difficulty in sleeping, irritability, anxiety, and depression [7], and has been shown to negatively influence cognitive functioning such as working memory and attention [8]. Tinnitus can occur due to a variety of causes but is most often associated with excessive noise exposure. The prevalence of tinnitus is particularly high in people returning from military service, and is much higher in people with severe to profound hearing loss. Of growing concern is the overexposure of young people to recreational sounds, considered a key driver of hearing loss and tinnitus.

There is emerging and concerning evidence that we may be underestimating the impact of noise exposure on our hearing. Relatively recent research in animal models of hearing loss has found that moderate levels of sound exposure can result in the loss of a subset of auditory nerves that send sound information to the brain, but sensitivity to sounds remains unchanged [9, 10]. This means (in this model at least) that there can be substantial neural damage but no measurable change in hearing thresholds (the lowest intensity that a sound can be detected). This finding has led many in the hearing research community to speculate that this also occurs in humans, and that people who have difficulty understanding speech, particularly in noisy situations, may be misdiagnosed as having ‘normal’ hearing. Routine clinical testing focusses on auditory sensitivity by measuring the detection of soft sounds under quiet conditions. However, many patients are told that despite their difficulty understanding speech they have normal auditory sensitivity [11] and there is nothing that can be done for them. In fact, many of these patients exhibit problems in processing the temporal (timing) information important for understanding complex sounds, but this is not routinely tested for, and hence are often referred to as having a ‘hidden hearing loss’ [12]. This example highlights three points. First, we have a significant knowledge gap at this point in time and only research will determine if this phenomenon in humans is equivalent to the pathologies observed in animal models. If this turns out to the case, it has massive implications for all Australians and how we manage noise levels in daily life and in the workplace. Second, if confirmed, there will be need to be changes in clinical practice and how hearing impairment is diagnosed. Finally, patients would benefit from a shift of focus from hearing sensitivity to focussing on the hearing disability.

The above text provides a very brief snapshot of the consequences of hearing impairment to Australians and our economy. Hearing impairment and deafness has far-reaching impacts on quality of life, language development and educational attainment in young Australians, social engagement and mental well-being in older Australians, and is associated with substantial economic costs in healthcare and lost productivity. In my experience, hearing health is also often

Page | 3 viewed as a ‘poor cousin’ compared to the value we place on our sight. Most people would not hesitate to get their eyes tested, wear glasses or contact lenses, and have 20/20 vision restored. In striking contrast, many older people will deny hearing impairment or just choose to endure it, only reluctantly wear a hearing aid (or receive one then not use it) and, importantly, ‘perfect’ hearing is not restored with current hearing aid technologies (although these are constantly improving through research and commercial R&D). This relegation of hearing as less important than vision is misguided, and is something that could be mitigated by government policy (as being addressed in this inquiry) and investment in research into hearing loss and ways to provide better diagnosis and therapies (see following section).

We strongly recommend that hearing health and wellbeing be considered as the next National Health Priority for Australia.

Developments in research into hearing loss including: prevention, causes, treatment regimes, and potential new technologies

The Bionics Institute develops innovative bionic health solutions through research. The goal of our bionic hearing research program is to improve the clinical outcomes for hearing device users and those with hearing loss. To achieve this goal we use a wide variety of experimental approaches from brain imaging and bioengineering to nanotechnology and gene therapy. We carry out clinical studies with research volunteers who use cochlear implants, as well as pre-clinical, lab-based research that determines the safety and effectiveness of potential new treatments and devices. The Institute collaborates with clinicians to ensure our research has clinical relevance, and also engages with industry to ensure there is a commercial pathway for new technologies.

Given our Institute’s history, approach and expertise, we can comment on recent research developments in the areas of “treatment regimes and potential new technologies”. The following provides a brief overview of some areas of ongoing research that will improve the quality of hearing provided by cochlear implants, and explore possible treatments for deafness and other hearing disorders.

Sensorineural hearing loss is the most common form of deafness and is typically due to damage to cells in the inner ear (cochlea). The delicate cells that sense the incoming sound waves (called hair cells) can die as a result of genetic factors, disease, excessive noise exposure, head injury, certain medications, and the aging process. In turn, this leads to the gradual degeneration of the nerve cells that send information to the brain (auditory neurons). Regardless of the cause, once these cells die, the hearing loss is permanent and irreversible. The cochlear implant is designed to bypass the damaged or missing hair cells and produce hearing sensations by direct electrical stimulation of the inner ear’s auditory neurons.

The development of the cochlear implant in the 1980s provided a significant step in the alleviation of the effects of severe/profound hearing loss (around 10% of adults with a loss).

Page | 4

Rapid technological advances in the following 20 years led to continual but dwindling improvements in outcomes. Relatively little progress has been made in the last 15 years, with a number of serious challenges limiting the potential benefits. A number of research programs are addressing ways to overcome these limitations.

• Variability in speech understanding in cochlear implant users. The quality of hearing provided by cochlear implants varies widely amongst users. While many users achieve very good speech understanding, a significant subset receives only a small benefit from their device. We are studying the changes in the organisation of the hearing and language parts of the brain in response to deafness and in response to the subsequent restoration of hearing via cochlear implantation. This will allow us to identify the contribution of brain reorganisation (neuroplasticity) to variable outcomes in speech understanding. Using a relatively new brain imaging technique that is compatible with implanted devices, we are identifying patterns of brain activity and connectivity associated with poor speech understanding outcomes. The aim is to develop a new clinical tool that will assist clinicians in advising cochlear implant candidates of likely outcomes (enabling better informed consent) and also to guide post- implantation therapies to optimise outcomes. • Cochlear implant programming is time-consuming and requires access to a specialist clinic. Following cochlear implantation a patient will visit their clinician to have the implant switched on and programmed. This means setting the levels of the electrical impulses sent to the cochlea so that the sounds heard are neither too soft nor too loud (fall within a ‘comfortable’ range). This is a time-consuming process that is not possible in those too young to provide verbal feedback. Our approach is to use an individual’s brain activity to determine when the sound is just audible. A new clinical system that provides automatic and objective programming of cochlear implants would have a number of benefits including enabling greater access to this technology in rural and remote areas, and enabling accurate programming in infants and young children. Programming implants in children is particularly important since we know early access to hearing is crucial for language development. • Many cochlear implant recipients have difficulties understanding speech in noisy environments. The basic anatomy of the inner ear is a major contributor to this limitation of electric hearing. The inner ear consists of fluid-filled chambers and allows spread of electrical current. This means that the information sent to the brain is crude compared to the digital signal being sent to the electrodes implanted in the cochlea. However, the way in which electrical stimulation is presented to the cochlea can be manipulated to counteract this current spread and effectively focus the current. This is an active area of research and it is important to note that any new stimulation strategy must be tested for safety before it can be trialled in patients. • Brain imaging studies will also help us understand what is happening in the brains of people who are experiencing difficulties in understanding speech but have ‘normal’ hearing thresholds (so-called ‘hidden hearing loss’; see previous section, p. 3). Research is aimed at identifying patterns of brain activity that are associated with this type of hearing impairment. This information is vital if we are to design and develop therapies to address this disability.

Page | 5

The effectiveness of cochlear implants depends on the survival of a critical number of auditory neurons. Many research groups globally are exploring ways to protect and repair the damaged cells of the inner ear, or even restore or replace cells that have died. Research at the Bionics Institute is exploring gene therapy, stem cell therapy, and nanoengineering as a means to do this.

• We can use the inner ear’s natural capacity for repair, but first we need a reliable and safe ‘trigger’ to start the process. Gene therapy has great potential to do this. Gene therapy has been successful in laboratory experiments: it can help the inner ear to produce natural factors that protect cells from degeneration after hearing loss. Additionally, gene therapy can ‘re- program’ some cells to appear and function like new sensory hair cells. We have introduced genes into the inner ear to trigger the production of neurotrophins (factors that support the health and survival of neurons) and transcription factors (capable of re-programming cells to perform a new function). Respectively, these studies have shown we can protect the auditory nerve from degeneration and create new hair-like cells following hearing loss. Ongoing research will help us understand the processes involved in hearing restoration and explore its limits. • Gene therapy may also provide a way to improve the selectivity of the stimulation provided by cochlear implants. As outlined above, some of the important features of complex sounds conveyed by the cochlear implant are lost due to the conductive nature of the fluid-filled cochlea. New techniques are required to overcome this inherent limitation and we are exploring gene technologies as a way to improve the precision of electrical stimulation. Specifically, we are using gene transfer techniques to render auditory neurons responsive to light (termed optogenetics) and will determine whether stimulating these neurons with light can deliver more precise activation than electrical stimulation. • Stem cell transplantation therapy is emerging as a potential strategy for auditory nerve rehabilitation by providing a source of replacement neurons to the deaf cochlea. Our aim is to use stem cells to understand and regenerate the auditory system after deafness. We use a number of different methods in the laboratory in order to turn our stem cell populations into the cells that we desire (hair cells or auditory neurons), to test their function (physiology), to measure the number and type of connections they make within auditory tissue, and to assess how well they integrate into the cochlea after they are transplanted. By helping us understand the molecular and genetic mechanisms of diseases affecting the auditory system, this research offers potential to discover new treatments for hearing loss. • We are using nanotechnology to provide long term and controlled delivery of therapeutic drugs in order to prevent progressive hearing loss. In laboratory experiments, we have shown that nanoparticles loaded with nerve survival factors (neurotrophins) can be introduced into the inner ear. These particles slowly release the neurotrophins, and we have found this protects auditory neurons against degeneration following deafness. The ultimate goal of this research is to provide a treatment to prevent progressive hearing loss. This treatment will also benefit the increasing number of cochlear implant recipients with residual hearing by allowing

Page | 6

them to gain maximum benefit from both electrical and natural hearing.

The above text provides a snapshot of some of the areas of interest to the Bionics Institute and those we believe will improve clinical practice and hearing outcomes for those receiving cochlear implants in the near future. It also provides some examples of ways the inner ear may be protected or even repaired following damage, as well as novel methods being explored to introduce therapeutic drugs into the inner ear.

References

[1] http://www.who.int/mediacentre/factsheets/fs300/en/

[2] http://apo.org.au/resource/listen-hear-economic-impact-and-cost-hearing-loss-australia

[3] Lin FR, Metter EJ, O’Brien RJ, Resnick SM, Zonderman AB, Ferrucci L. Hearing loss and incident dementia. Arch Neurol, 2011; 68(2): 214-220. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3277836/#__ffn_sectitle

[4] The Consequences of Untreated Hearing Loss in Older Adults. National Council of Aging, 1999. Available at: https://www.ncoa.org/resources/the-consequences-of-untreated-hearing-loss-in-older-adults/

[5] Li C-M, Zhang X, Hoffman HJ, Cotch MF, Themann CL, Wilson MR. Hearing Impairment Associated With Depression in US Adults, National Health and Nutrition Examination Survey 2005-2010. JAMA Otolaryngol Head Neck Surg, 2014, 140(4): 293-302. doi:10.1001/jamaoto.2014.42

[6] Kong K, Coates HLC. Natural history, definitions, risk factors and burden of otitis media. Med J Aust, 2009, 191(9): 39. Available at: https://www.mja.com.au/journal/2009/191/9/natural-history-definitions- risk-factors-and-burden-otitis-media

[7] Dobie RA. Depression and tinnitus. Otolaryngol Clin North Am, 2003, 36: 383-8.

[8] Rossiter S, Stevens C, Walker G. Tinnitus and its effect on working memory and attention. J Speech Lang Hear Res, 2006, 49: 150-60.

[9] Kujawa SG, Liberman MC. Adding insult to injury: cochlear nerve degeneration after “temporary” noise- induced hearing loss. J Neurosci, 2009, 29: 14077-14085.

[10] Lin HW, Furman AC, Kujawa SG, Liberman MC. Primary neural degeneration in the Guinea pig cochlea after reversible noise-induced threshold shift. JARO, 2011, 12: 605-16.

[11] Shinn-Cunningham B, Ruggles DR, Bharadwaj H. How early aging and environment interact in everyday listening: from brainstem to behavior through modeling. In: Basic Aspects of Hearing, Springer. 2013, p. 501-510.

[12] Plack CJ, Barker D, Prendergast, G. Perceptual consequences of "hidden" hearing loss. Trends in Hearing, 2014, 18: 1-11.

Page | 7