Is There an Unmet Medical Need for Improved Hearing Restoration?

Overview

Journal EMBO Mol Med

Specialty Molecular Biology

Date 2022 Jul 14

PMID 35833443

Authors

Bettina Julia Wolf

Kathrin Kusch

Victoria Hunniford

Barbara Vona

Robert Kuhler

Daniel Keppeler

Nicola Strenzke

Tobias Moser

Affiliations

Soon will be listed here.

Abstract

Hearing impairment, the most prevalent sensory deficit, affects more than 466 million people worldwide (WHO). We presently lack causative treatment for the most common form, sensorineural hearing impairment; hearing aids and cochlear implants (CI) remain the only means of hearing restoration. We engaged with CI users to learn about their expectations and their willingness to collaborate with health care professionals on establishing novel therapies. We summarize upcoming CI innovations, gene therapies, and regenerative approaches and evaluate the chances for clinical translation of these novel strategies. We conclude that there remains an unmet medical need for improving hearing restoration and that we are likely to witness the clinical translation of gene therapy and major CI innovations within this decade.

Citing Articles

Optogenetically modified human embryonic stem cell-derived otic neurons establish functional synaptic connection with cochlear nuclei.

Chen Y, Mu W, Wu Y, Xu J, Li X, Hu H J Tissue Eng. 2024; 15:20417314241265198.

PMID: 39092452 PMC: 11292720. DOI: 10.1177/20417314241265198.

Catching up but still miles behind-a patient registry for otoferlin.

Vona B, Wollnik B, Strenzke N, Moser T Exp Mol Med. 2024; 56(6):1472-1473.

PMID: 38825639 PMC: 11263334. DOI: 10.1038/s12276-024-01247-6.

Gene therapy for deafness: are we there now?.

Moser T, Chen H, Kusch K, Behr R, Vona B EMBO Mol Med. 2024; 16(4):675-677.

PMID: 38528140 PMC: 11018804. DOI: 10.1038/s44321-024-00058-6.

Clarin-2 gene supplementation durably preserves hearing in a model of progressive hearing loss.

Mendia C, Peineau T, Zamani M, Felgerolle C, Yahiaoui N, Christophersen N Mol Ther. 2024; 32(3):800-817.

PMID: 38243601 PMC: 10928142. DOI: 10.1016/j.ymthe.2024.01.021.

MSC-derived exosomes protect auditory hair cells from neomycin-induced damage via autophagy regulation.

Liu H, Kuang H, Wang Y, Bao L, Cao W, Yu L Biol Res. 2024; 57(1):3.

PMID: 38217055 PMC: 10787390. DOI: 10.1186/s40659-023-00475-w.

References

Fettiplace R . Hair Cell Transduction, Tuning, and Synaptic Transmission in the Mammalian Cochlea. Compr Physiol. 2017; 7(4):1197-1227. PMC: 5658794. DOI: 10.1002/cphy.c160049. View

Tan X, Rajguru S, Young H, Xia N, Stock S, Xiao X . Radiant energy required for infrared neural stimulation. Sci Rep. 2015; 5:13273. PMC: 4548241. DOI: 10.1038/srep13273. View

Montero-Odasso M, Ismail Z, Livingston G . One third of dementia cases can be prevented within the next 25 years by tackling risk factors. The case "for" and "against". Alzheimers Res Ther. 2020; 12(1):81. PMC: 7346354. DOI: 10.1186/s13195-020-00646-x. View

Wolf B, Kusch K, Hunniford V, Vona B, Kuhler R, Keppeler D . Is there an unmet medical need for improved hearing restoration?. EMBO Mol Med. 2022; 14(8):e15798. PMC: 9358394. DOI: 10.15252/emmm.202215798. View

Teudt I, Maier H, Richter C, Kral A . Acoustic events and "optophonic" cochlear responses induced by pulsed near-infrared laser. IEEE Trans Biomed Eng. 2011; 58(6):1648-55. PMC: 3449328. DOI: 10.1109/TBME.2011.2108297. View

Moser T . Optogenetic stimulation of the auditory pathway for research and future prosthetics. Curr Opin Neurobiol. 2015; 34:29-36. DOI: 10.1016/j.conb.2015.01.004. View

Ahmed H, Shubina-Oleinik O, Holt J . Emerging Gene Therapies for Genetic Hearing Loss. J Assoc Res Otolaryngol. 2017; 18(5):649-670. PMC: 5612923. DOI: 10.1007/s10162-017-0634-8. View

Gao X, Tao Y, Lamas V, Huang M, Yeh W, Pan B . Treatment of autosomal dominant hearing loss by in vivo delivery of genome editing agents. Nature. 2017; 553(7687):217-221. PMC: 5784267. DOI: 10.1038/nature25164. View

Zeng F . Challenges in Improving Cochlear Implant Performance and Accessibility. IEEE Trans Biomed Eng. 2017; 64(8):1662-1664. PMC: 5586220. DOI: 10.1109/TBME.2017.2718939. View

10.

Moser T, Starr A . Auditory neuropathy--neural and synaptic mechanisms. Nat Rev Neurol. 2016; 12(3):135-49. DOI: 10.1038/nrneurol.2016.10. View

11.

Mager T, Lopez de la Morena D, Senn V, Schlotte J, D Errico A, Feldbauer K . High frequency neural spiking and auditory signaling by ultrafast red-shifted optogenetics. Nat Commun. 2018; 9(1):1750. PMC: 5931537. DOI: 10.1038/s41467-018-04146-3. View

12.

Rankovic V, Vogl C, Dorje N, Bahader I, Duque-Afonso C, Thirumalai A . Overloaded Adeno-Associated Virus as a Novel Gene Therapeutic Tool for Otoferlin-Related Deafness. Front Mol Neurosci. 2021; 13:600051. PMC: 7817888. DOI: 10.3389/fnmol.2020.600051. View

13.

Bowl M, Dawson S . Age-Related Hearing Loss. Cold Spring Harb Perspect Med. 2018; 9(8). PMC: 6671929. DOI: 10.1101/cshperspect.a033217. View

14.

Maeder M, Stefanidakis M, Wilson C, Baral R, Barrera L, Bounoutas G . Development of a gene-editing approach to restore vision loss in Leber congenital amaurosis type 10. Nat Med. 2019; 25(2):229-233. DOI: 10.1038/s41591-018-0327-9. View

15.

Tang P, Hashino E, Nelson R . Progress in Modeling and Targeting Inner Ear Disorders with Pluripotent Stem Cells. Stem Cell Reports. 2020; 14(6):996-1008. PMC: 7355141. DOI: 10.1016/j.stemcr.2020.04.008. View

16.

Duman D, Tekin M . Autosomal recessive nonsyndromic deafness genes: a review. Front Biosci (Landmark Ed). 2012; 17(6):2213-36. PMC: 3683827. DOI: 10.2741/4046. View

17.

Nagel G, Szellas T, Huhn W, Kateriya S, Adeishvili N, Berthold P . Channelrhodopsin-2, a directly light-gated cation-selective membrane channel. Proc Natl Acad Sci U S A. 2003; 100(24):13940-5. PMC: 283525. DOI: 10.1073/pnas.1936192100. View

18.

Shannon R . Multichannel electrical stimulation of the auditory nerve in man. II. Channel interaction. Hear Res. 1983; 12(1):1-16. DOI: 10.1016/0378-5955(83)90115-6. View

19.

Effertz T, Moser T, Oliver D . Recent advances in cochlear hair cell nanophysiology: subcellular compartmentalization of electrical signaling in compact sensory cells. Fac Rev. 2021; 9:24. PMC: 7886071. DOI: 10.12703/r/9-24. View

20.

Chen J, Hong F, Zhang C, Li L, Wang C, Shi H . Differentiation and transplantation of human induced pluripotent stem cell-derived otic epithelial progenitors in mouse cochlea. Stem Cell Res Ther. 2018; 9(1):230. PMC: 6116394. DOI: 10.1186/s13287-018-0967-1. View