Repairing Cochlear Damage with Neurotrophin Therapy
Abstract
Hearing loss affects hundreds of millions of people worldwide and is the most common disability in developed countries. It has a significant personal impact on individuals, as well as substantial economic costs in terms of lost productivity and healthcare. Hearing loss not only impacts our ability to communicate with loved ones, but is associated with cognitive decline, social isolation, and depression. In the US alone, the economic cost of hearing loss has been estimated at $122 billion to $186 billion per year -- a cost that is rising with the aging population. The need to develop a therapeutic intervention to treat hearing loss is a high priority; the most effective strategy would be to repair inner ear damage before it becomes a debilitating condition. Around one-third of hearing loss cases is related to noise exposure, with an estimated 22 million Americans experiencing potentially damaging levels of noise in their workplace. The inner ear, or cochlea, can sustain significant injury well before a person notices a change in hearing thresholds (e.g., a change in the softest sound that can be heard). It is becoming clear that most adults have damage to the connections (synapses) between the cochlea s delicate sensory (hair) cells and the auditory nerve cells that transmit sound information to the brain. Inner ear damage is likely due to accumulated moderate noise exposure throughout life, and the consequence is typically noticeable in difficult listening conditions (e.g., at a noisy restaurant or party). Noise-induced damage can also accumulate due to repeated, short-term exposure to high levels of noise, as experienced in some professions (e.g., military service, factory workers). Unfortunately, inner ear damage and its effects are likely to worsen over time as more hair cells and their connections are lost: once established, hearing loss is a permanent impairment that places a continuing burden on the individual, the community, and the healthcare system. What if we could repair the lost connections in the cochlea? There is compelling experimental evidence that delivering nerve survival factors (called neurotrophins) to the cochlea can restore synapses following noise exposure. However, in order to translate these experimental findings into a clinical treatment, we need to develop an effective and safe way to deliver neurotrophins into the cochlea over a long and clinically relevant period of time. Researchers at The Bionics Institute of Australia have been working on different drug delivery methods for several years and we have made significant advances. In collaboration with colleagues at the University of Melbourne, we have developed a novel way to deliver neurotrophins by "loading" them into particles created through nanoengineering (called supraparticles). Before we can undertake a clinical trial of our neurotrophin therapy we must determine the following: (i) How neurotrophins disperse in the inner ear and whether therapeutic amounts of neurotrophins are reaching the cells that will benefit; (ii) Do supraparticles or their therapeutic load spread outside the inner ear (are they safe)? (iii) Does the therapy work by re-establishing meaningful improvements in how we process sound? and (iv) Confirm that the neurotrophin therapy rescues synapses and hearing function. The proposed project will bring us a critical step closer to a clinical trial of a safe and effective drug treatment for those living with noise-induced hearing loss. The first patient-related outcomes could be achieved within a few years after the completion of this study. Following the proposed 3-year study, it will take approximately 1 year to develop a manufacturing protocol and complete toxicology experiments required for regulatory approvals, and a further 3 months for ethical approvals before a clinical trial can commence. We would expect that initial outcomes in five patients would be achievable within the first 12 months of a clinical
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810276
Entities
People
- Andrew K. Wise
Organizations
- Bionics Institute
- United States Army