Emerging therapies for human hearing loss

ABSTRACT

Introduction

More than 5% of the world’s population have a disabling hearing loss which can be managed by hearing aids or implanted electrical devices. However, outcomes are highly variable, and the sound perceived by recipients is far from perfect. Sparked by the discovery of progenitor cells in the cochlea and rapid progress in drug delivery to the cochlea, biological and pharmaceutical therapies are currently in development to improve the function of the cochlear implant or eliminate the need for it altogether.

Areas covered

This review highlights progress in emerging regenerative strategies to restore hearing and adjunct therapies to augment the cochlear implant. Novel approaches include the reprogramming of progenitor cells to restore the sensory hair cell population in the cochlea, gene therapy, and gene editing to treat hereditary and acquired hearing loss. A detailed review of optogenetics is also presented as a technique that could enable optical stimulation of the spiral ganglion neurons, replacing or complementing electrical stimulation.

Expert opinion

Increasing evidence of substantial reversal of hearing loss in animal models, alongside rapid advances in delivery strategies to the cochlea and learnings from clinical trials will amalgamate into a biological or pharmaceutical therapy to replace or complement the cochlear implant.

KEYWORDS:

• Cell-based therapy
• cochlear implant
• hair cell
• hearing loss
• gene therapy
• optogenetics
• regeneration
• spiral ganglion neuron

Article highlights

• There is currently no approved pharmaceutical or biological therapy to reverse hearing loss

• A number of preclinical studies have shown improved auditory function through the preservation or regeneration of cochlear sensory cells by various strategies based on the pathology of hearing loss

• Genetic and pharmacologic manipulation of the Notch and Wnt signalling pathways result in regeneration of cochlear hair cells

• Application of neurotrophic factors to the cochlea can repair the hair cell ribbon synapse that is damaged by noise over-exposure

• Effective reversal of hearing loss has been demonstrated via timely application of gene therapy to introduce normal copies of genes into cells or gene editing techniques for targeted gene disruption or repair of mutations

• Strategies to improve cochlear implant function include improving the nerve–electrode interface and using optogenetics to make neurons responsive to light to allow the use of optical cochlear implants

This box summarizes key points contained in the article.

Declaration of interest

E Ajay receives a scholarship through the University of Melbourne, Department of Engineering. R Richardson receives funding from the National Health and Medical Research Council (GNT2002523) and has a published patent (WO2020257864A1). N Gunewardene receives funding from the National Health and Medical Research Council (Development Grant 2000202) and has a published patent (WO2020112883A1). 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 apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by the National Health and Medical Research Council (GNT2002523; Development Grant 2000202) and the University of Melbourne, Department of Engineering. The Bionics Institute acknowledges the support it receives from the Victorian Government through its Operational Infrastructure Support Program.