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  • Review Article
  • Published:

New treatment options for hearing loss

Nature Reviews Drug Discovery volume 14, pages 346–365 (2015)Cite this article

Subjects

Key Points

  • Hearing loss is the most common form of sensory impairment in humans and manifests in many forms, ranging from deafness at birth to slow progressive hearing loss during the ageing process.

  • Hearing loss is caused by both genetic and environmental factors.

  • Treatment options for hearing loss are mostly based on medical devices, including hearing aids and cochlear implants; there are no pharmacological therapeutics currently in widespread use.

  • Hair cells in the inner ear are the sensory cells for the detection of sound; hair cells are frequently affected in different forms of hearing loss and they are a common target for therapeutic intervention in various forms of the disease.

  • The study of genes that are affected in patients suffering from hearing loss has identified molecular pathways that are potential therapeutic targets.

  • Hair cells have been generated in vitro from stem cells and hold great potential for drug screens and possibly for regenerative medicine.

  • Gene therapy has successfully been used to treat hearing loss in animal model systems.

  • Different forms of hearing loss, such as noise- and age-related forms, share pathological features, which raises the possibility that similar approaches and pharmacological therapeutics might be useful to treat different forms of the disease.

Abstract

Hearing loss is the most common form of sensory impairment in humans and affects more than 40 million people in the United States alone. No drug-based therapy has been approved by the Food and Drug Administration, and treatment mostly relies on devices such as hearing aids and cochlear implants. Over recent years, more than 100 genetic loci have been linked to hearing loss and many of the affected genes have been identified. This understanding of the genetic pathways that regulate auditory function has revealed new targets for pharmacological treatment of the disease. Moreover, approaches that are based on stem cells and gene therapy, which may have the potential to restore or maintain auditory function, are beginning to emerge.

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Figure 1: The auditory sensory organ.
Figure 2: Evaluation of hearing function in mice.
Figure 3: Analysis of hair bundle morphology in mouse models.
Figure 4: Production of hair cells.
Figure 5: Common defects in hearing loss and potential therapeutic approaches.

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Acknowledgements

This work was supported by NIH grants R01 DC002368 (P.B-G.), R01 DC011034 (P.B-G.), R01 DC005965 (U.M.) and RO1 DC007704 (U.M.); fellowship support from the Hearing Health Foundation (P.B-G); the Dorris Neuroscience Center (U.M.), the Skaggs Institute for Chemical Biololgy (U.M.) and the California Institute of Regenerative Medicine (U.M.).

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Authors and Affiliations

  1. Department of Molecular and Cellular Neuroscience, Dorris Neuroscience Center, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, San Diego, 92037, California, USA

    Ulrich Müller

  2. Oregon Hearing Research Center, Vollum Institute, Oregon Health & Science University, 3181 South West Sam Jackson Park Road, Portland, 97239, Oregon, USA

    Peter G. Barr-Gillespie

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  1. Ulrich Müller
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Correspondence to Ulrich Müller or Peter G. Barr-Gillespie.

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Glossary

Nonsyndromic deafness

A genetic form of hearing loss that affects hearing function without any other symptoms in different tissues and organs.

Syndromic deafness

A genetic form of hearing loss that affects not only hearing but also the function of other tissues and organs.

Ototoxic

A substance that is toxic to the ear, such as certain antibiotics and chemotherapy agents.

Tinnitus

Perception of a ringing tone within the ear without an external sound trigger.

Cochlear implants

Electrical medical devices that are implanted into the cochlea as a substitute for the function of damaged hair cells.

Organ of Corti

The end-organ in the inner ear that functions in sound perception.

Outer hair cells

(OHCs). Sensory cells for sound perception that are required to amplify input sound signals for their subsequent detection and processing by inner hair cells.

Inner hair cells

Sensory cells that transmit sound information via neurons to the nervous system.

Tectorial membrane

An acellular membrane of the inner ear that covers the mechanically sensitive hair bundles of hair cells and is required for the transmission of mechanical signals that are evoked by sound stimuli.

Basilar membrane

A stiff acellular structure of the inner ear that underlies the sensory epithelium and resonates in response to sound-induced mechanical signals.

Tympanic membrane

A membrane that separates the external from the middle ear, also referred to as the eardrum.

Ossicles

The three bones of the middle ear that transmit sound information from the external ear to the cochlea in the inner ear.

Synapses

Structural specializations that allow signal transmission between neurons or from sensory cells, such as hair cells, to neurons.

Hypomorphic alleles

Alleles of genes that reduce the activity of the gene or of its gene product.

Reactive oxygen species

(ROS). Chemically reactive molecules that contain oxygen and have important functions for cell signalling, but in excessive amounts can cause tissue damage.

Endolymph

The fluid within the membranous labyrinth of the inner ear that bathes the stereocilia of hair cells.

Gap junctions

Specialized intracellular junctions that connect the cytoplasm of two cells and enable the passage of molecules and ions between them.

Fibrocytes

Mesenchymal cells that are distributed throughout the inner ear and are thought to be involved in K+ recycling.

Stria vascularis

A secretory epithelium of the inner ear that produces and secretes endolymph and also sets the endocochlear potential.

Temporary threshold shift

A temporary, recoverable loss in sensitivity to sound.

Permanent threshold shift

Permanent loss in the sensitivity to sound.

Aminoglycoside antibiotics

Antibacterial drugs directed against Gram-negative bacteria that inhibit protein synthesis.

Apoptosis

Programmed cell death that relies on the activation of a cascade of events, which are genetically encoded.

Single nucleotide polymorphisms

(SNPs). Variation in DNA sequences in which a single nucleotide differs in the genome between members of a species.

Audiogram

A graph that represents the response of the auditory system to a range of standardized frequencies and intensities, which is used to determine the sensitivity of the auditory system to sound.

Genome-wide association studies

(GWAS). A methodology that scans markers across the entire genome to identify genetic variations that are associated with genetic traits, including susceptibility to hearing loss.

Serotypes

Groups of viruses or microorganisms that can be distinguished by shared specific antigens, which are determined by serological tests.

Pillar cells

Supporting cells within the sensory epithelium of the inner ear that form the walls of a fluid-filled tunnel between the inner and outer hair cells.

Deiters' cells

Supporting cells within the sensory epithelium of the inner ear that sit on the basilar membrane and hold the base of outer hair cells. They also form apical processes that extend next to the apical surfaces of outer hair cells.

Auditory brain stem response

Electrical potentials that are measured with electrodes placed on the scalp while the ear is stimulated with sound of defined intensity and frequency using a loudspeaker.

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Müller, U., Barr-Gillespie, P. New treatment options for hearing loss. Nat Rev Drug Discov 14, 346–365 (2015). https://doi.org/10.1038/nrd4533

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