Protecting and regenerating hair cells with gene therapy


An estimated 360 million people suffer from hearing loss worldwide. As the population ages, the prevalence of hearing loss is expected to rise. There are currently no approved drugs on the market for hearing loss despite recent advances in our understandings of hearing loss and the capacity of the cochlea for repair and regeneration.

Gene therapy in particular is showing promise as a method to deliver the factors to the cochlea necessary for hair cell repair and regeneration. New hair cells can be formed after hearing loss via gene therapy with a transcription factor called Atoh1, but despite more than 15 years of research there have been very few reports of recovery of hearing in adult mammals. We are studying the effect of cochlear pathology on hair cell formation using in vitro and in vivo gene therapy techniques.

Our research

We are using adenoviral vectors to introduce the Atoh1 gene into residual hair cells and supporting cells of the cochlea after hearing loss. We have examined Atoh1 gene therapy after a range of cochlear pathologies from sudden complete hair cell loss to progressive, partial hair cell loss. Induced hair cells were formed in all cases with the progressive models of hearing loss showing a greater window of opportunity for successful transgene expression. Hearing was not restored due in part to severe disruption of normal cellular patterning, and we are doing further work to examine Atoh1 gene therapy after more moderate hearing loss pathologies.

Efforts towards hair cell regeneration in the cochlea are also hampered by low transduction efficiency. This may have several contributing factors such as injection route, pathology in the cochlea and type of viral vector used.

Our work has focussed on the critical need to improve cellular targeting and expression. We have used two techniques for cellular targeting of gene therapy: direct injection into the scala media of the cochlea and cell specific promoters. Although injection into the scala media efficiently targeted hair cells and supporting cells in the organ of Corti and resulted in induced hair cell formation, there was non-specific expression in some other cell types and unacceptable hearing loss associated with the technique.

Furthermore, specific targeting of hair cells or supporting cells will be necessary to develop molecular therapies for hair cell repair or regeneration, respectively.

Research team

Principal investigators –¬†Dr Rachael Richardson, Dr Andrew Wise


NHMRC, Action on Hearing Loss (UK), The Garnett Passe and Rodney Williams Memorial Foundation

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