Project 462258

Today, there are no cures for hearing loss and balance disorders. Our research will generate molecular information that we will use in preclinical studies. Inner ear sensory cells detect sound and movement enabling us to hear and maintain balance. Their loss, mainly due to aging, leads to permanent deficits causing inner ear disorders as sensory cells do not spontaneously regenerate. Almost 80% of Canadians aged 60+ have mild-to-severe hearing loss, and 35% aged 40+ will experience a balance disorder like vertigo. With a doubling of the elderly population by 2050, it is expected that these disorders will reach epidemic proportions. This will have a profound impact on the quality of life with an increased economic cost for elder care. People with hearing loss have up to five times higher risk of developing depression and dementia including Alzheimer's disease. About 50% of people with balance disorders could develop mental illness. Therefore, inner ear disorders are the largest modifiable risk factor for these life-altering conditions. These data highlight a pressing need for biological solutions for treating these progressive and permanent disorders. One main reason for the lack of treatments is that human inner ear genes, their activities, as well as molecular networks that control them, have not been identified. We know that under certain experimental conditions the inner ear organs can regenerate their sensory cells at early developmental stages, but this ability is lost at later stages. Therefore, we will use sequencing technologies to identify genes and molecular mechanisms that control this process at early and late stages in human inner ear organs. Once genes and pathways are revealed, we will test their effectiveness as therapeutic targets in inducing regeneration directly in human inner ear models. By targeting key gene regulators, we will lay the groundwork for gene therapy studies, accelerating potential cures for people with inner ear disorders.