Atoh1 gene therapy in the cochlea for hair cell regeneration

Abstract

Introduction: The sensory epithelium of the cochlea is a complex structure containing hair cells, supporting cells and auditory nerve endings, all of which degenerate after hearing loss in mammals. Biological approaches are being considered to preserve and restore the sensory epithelium after hearing loss. Of particular note is the ectopic expression of the Atoh1 gene, which has been shown to convert residual supporting cells into hair cells with restoration of function in some cases.

Areas covered: In this review, hair cell development, spontaneous regeneration and hair cell regeneration mediated by Atoh1 gene therapy in the cochlea are discussed.

Expert opinion: Gene therapy can be safely delivered locally to the inner ear and can be targeted to the sensory epithelium of the cochlea. Expression of the Atoh1 gene in supporting cells results in their transformation into cells with the appearance and function of immature hair cells but with the resulting loss of the original supporting cell. While the feasibility of Atoh1 gene therapy in the cochlea is largely dependent on the severity of the hearing loss, hearing restoration can be achieved in some situations. With further advances in Atoh1 gene therapy, hearing loss may not be as permanent as once thought.

Keywords:

• adenovirus
• atoh1
• cochlea
• gene therapy
• hair cell
• hearing loss
• regeneration
• supporting cell

Declaration of interest

P Atkinson has received research funding from the US Department of Health and Human Services-National Institutes of Health. R Richardson has received funding from Action on Hearing Loss (G39), the Garnett Passe and Rodney Williams Memorial Foundation and the National Health and Medical Research Council (GNT1024350). The Bionics Institute acknowledges the support it receives from the Victorian Government through its Operational Infrastructure Support Program. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Notes

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