Determining the limits for reversing hearing loss

Progressive hearing loss is very common but there are no medical treatments to slow down or reverse it. Histopathological reports suggest three main sites of lesion in the cochlea can be involved: sensory hair cells; synapses of hair cells with cochlear neurons; and the stria vascularis which produces a potassium-rich fluid with an endocochlear potential of +100mV that is essential for hair cell sensitivity. This research has three goals that will provide the scientific underpinning for development of new treatments for hearing loss. Firstly, we will investigate whether hearing loss in each of the three pathological categories can be reversed and hearing improved. Secondly, the research will determine what the limiting factors to reversal of hearing loss are and how these define the critical period for intervention. Thirdly, we will develop new diagnostic tools to distinguish the three sites of lesion using objective measures of auditory responses, to establish the underlying pathological contributions to hearing loss in an individual, and hence determine the optimum treatment. To achieve these goals, we will use mouse mutants with well-characterised cochlear pathology as examples of each site of lesion, and a new approach to reactivating a mutant gene after the onset of hearing loss.