Drug development for noise-induced hearing loss

ABSTRACT

Introduction

Excessive exposure to noise is a common occurrence that contributes to approximately 50% of the non-genetic hearing loss cases. Researchers need to develop standardized preclinical models and identify molecular targets to effectively develop prevention and curative therapies.

Areas covered

In this review, the authors discuss the many facets of human noise-induced pathology, and the primary experimental models for studying the basic mechanisms of noise-induced damage, making connections and inferences among basic science studies, preclinical proofs of concept and clinical trials.

Expert opinion

Whilst experimental research in animal models has helped to unravel the mechanisms of noise-induced hearing loss, there are often methodological variations and conflicting results between animal and human studies which make it difficult to integrate data and translate basic outcomes to clinical practice. Standardization of exposure paradigms and application of -omic technologies will contribute to improving the effectiveness of transferring newly gained knowledge to clinical practice.

KEYWORDS:

• Animal models
• cochlear injury
• deafness
• hidden hearing loss
• NIHL
• preclinical research
• ROS
• synaptopathy

Acknowledgments

The authors wish to warmly thank our colleagues from the Neurobiology of Hearing group for sharing unpublished data and for helpful discussions, and Mr. Miguel Sánchez for preparing the illustrations.

Article highlights

• NIHL, the second most common form of deafness, has a high impact on quality of life and is a public health priority.

• Noise-induced hearing damage outcomes are influenced by the interaction of genetic and environmental factors, and include HL, tinnitus, hyperacusis, and vestibular alterations.

• HL is mainly produced by sensory hair cell death, while additional alterations to the hair bundles, the cochlear lateral wall or synapses could lead to auditory impairment.

• Underlying molecular mechanisms of NIHL include oxidative stress, inflammation, glutamate excitotoxicity, and calcium imbalance, which ultimately lead to activation of cell death pathways in sensory hair cells.

• Animal models are essential tools for identifying key molecular targets and developing new pharmacological approaches to prevent, ameliorate or treat NIHL.

This box summarizes key points contained in the article.

Declaration of interest

S Murillo-Cuesta holds a CIBER ISCIII research contract. 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.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported by the grants Multi Target and View FEDER/CM-B2017/BMD-3688 from the Consejería de Educación e Investigación, Comunidad de Madrid and MINECO/FEDER SAF2017-86107-R from the Ministerio de Economía, Industria y Competitividad, Gobierno de España.