The α9α10 nicotinic acetylcholine receptor: a compelling drug target for hearing loss?

ABSTRACT

Introduction

Hearing loss is a major health problem, impacting education, communication, interpersonal relationships, and mental health. Drugs that prevent or restore hearing are lacking and hence novel drug targets are sought. There is the possibility of targeting the α9α10 nicotinic acetylcholine receptor (nAChR) in the prevention of noise-induced, hidden hearing loss and presbycusis. This receptor mediates synaptic transmission between medial olivocochlear efferent fibers and cochlear outer hair cells. This target is key since enhanced olivocochlear activity prevents noise-induced hearing loss and delays presbycusis.

Areas covered

The work examines the α9α10 nicotinic acetylcholine receptor (nAChR), its role in noise-induced, hidden hearing loss and presbycusis and the possibility of targeting. Data has been searched in Pubmed, the World Report on Hearing from the World Health Organization and the Global Burden of Disease Study 2019.

Expert opinion

The design of positive allosteric modulators of α9α10 nAChRs is proposed because of the advantage of reinforcing the medial olivocochlear (MOC)-hair cell endogenous neurotransmission without directly stimulating the target receptors, therefore avoiding receptor desensitization and reduced efficacy. The time is right for the discovery and development of α9α10 nAChRs targeting agents and high throughput screening assays will support this.

KEYWORDS:

• Α9α10 nicotinic receptors
• hearing loss
• positive allosteric modulators
• presbycusis
• tinnitus

Article highlights

• Hearing loss is one of the most prevalent sensory disabilities. It is a major public health problem, given that its impact on human communication and quality of life is devastating.

• Within the environmental or lifestyle preventable factors that contribute the most to hearing loss is the exposure to elevated noise, which can be of occupational, recreational, or environmental origin.

• Several drugs have been investigated and/or used in the treatment of noise-induced hearing loss; a spectrum of outcomes has been observed, and there is poor evidence to support their use.

• The protective effect of the medial olivocochlear system from acute and chronic noise-induced hearing loss has been described in animal models. Thus, enhancing the strength of the MOC system appears is a means to protect from noise-induced hearing loss.

• Since the α9α10 nAChR mediates synaptic transmission between MOC fibers and cochlear hair cells, it appears to be a novel target for the development of drugs that prevent noise-induced hearing loss.

• The development of positive allosteric modulators of α9α10 nAChRs is proposed as a novel approach in the prevention from hearing disorders produced by exposure to loud sounds.

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Declaration of interest

The authors have no 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.

Reviewer disclosures

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

Additional information

Funding

This work was supported by the Agencia Nacional de Promoción Científica y Técnica and Scientific Grand Prize from the Fondation Pour L’ Audition, NIH grant R01 DC001508.