Protection against apoptosis in presbycusis and noise/drug induced hearing loss by cochlear transfection of xiap gene in experimental animals

The receptor cells (the hair cells) and neurons in mammalian ears degenerate with aging. This degeneration is enhanced by damaging factors such as noise and ototoxic drugs. Hair cell death due to aging and many other factors occurs mainly through a process called apoptosis, in which the cell commits "suicide" due to the production of several "killer proteins". Normally, cells contain specific inhibitors of apoptosis proteins (IAPs) which control these killer proteins. However, natural levels of these inhibitors do not seem sufficient to protect inner ear hair cells and neurons against apoptosis. In our previous study supported by CIHR, we proved that the over-expression of X-linked inhibitory of apoptotic protein (XIAP) in a transgenic mouse model significantly delay the development of aging-related hearing loss and provide protection against the hearing loss induced by noise and ototoxic drugs. Therefore, we will extend our study by using inner-ear gene transfection, instead of genetic manipulation at genome level, which is not ethic for humans. This project will explore optimal methods for gene transfection into inner ears of experimental animals. After a sufficient expression of xiap gene in the targeted cells in inner ears is established, we will evaluate if the over-expression of XIAP in inner ears provide similar protections as that seen in the transgenic mice. This research will potentially lead a gene therapy for the inner protection.