New avenues towards prevention of hearing loss

The cochlea is the organ of the inner ear essential for hearing. It is embedded in the skull and converts sound waves into electrical impulses transmitted to the brain. Central to this process are cochlear hair cells, which produce electrical signals in response to sound. Hair cells cannot regenerate if lost due to age or injury, and a steady decrease in their numbers over time underpins presbycusis, the propensity for people to lose their hearing as they age. Hair cells can also be destroyed if they are over-stimulated by prolonged loud noise during work or recreation, or are exposed to bacterial or viral infection. Additionally, iatrogenic hearing loss caused by medical interventions is commonly associated with surgery (particularly cochlear implant surgery); cancer treatment via platinum-based chemotherapies; radiation therapy in head and neck cancers; and antibiotic use. The irrevocable and debilitating nature of hearing loss as a side effect means that many promising treatments are under-utilised in the clinic. The cellular responses invoked in different forms of hearing loss (presbycusis, noise-induced, pathogenic, and iatrogenic) all result in hair cell injury. Therefore, new treatments that protect hair cells promise to transform clinical practice, and improve the quality of life in ageing populations. We have identified a protease normally present in cochlear cells that is responsible for the pathology of hair cell loss and hearing deterioration following stress. Strikingly, mutant mice lacking the protease display better hearing than normal, and resist hair cell loss and hearing deterioration caused by loud noise. These results strongly suggest that this protease mediates stress-induced hair cell damage and hearing loss, and that it is a novel therapeutic target. Blocking its function will preserve hearing in settings such as presbycusis, and following acute or chronic trauma. Project areas include examination of the normal role of the protease in the inner ear; and the development and testing of new protease inhibitors with therapeutic potential.