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Author Notes:

Correspondence: Xi Lin, xlin2@emory.edu

All authors listed have made a substantial, direct, and intellectual contribution to the work, and approved it for publication.

More specifically, WZ and XL designed and generated Figures ​Figures11–3, and made substantial contributions to the generation of all the Tables and Supplemental Tables.

SK, WW, and CC made substantial contributions to the generation of all the Tables and Supplemental Tables.

We thank three reviewers for carefully reading the manuscript.

Their comments have greatly helped in improving the quality of the review.

We also thank Ms. Anne Lin and Dr. Douglas Mattox for proofreading the manuscript carefully.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Subjects:

Research Funding:

This study was supported by grants to XL from the National Institute on Deafness and other Communication Disorders (RO1 DC006483 and RO1 DC014496).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • cochlear gene therapy
  • review
  • viral-mediated gene expression
  • preclinical trials
  • hearing restoration
  • sensorineural hearing loss
  • genetic mutations
  • genetic deafness
  • RENAL TUBULAR-ACIDOSIS
  • MAMMALIAN INNER-EAR
  • MOUSE MODEL
  • CONGENITAL AMAUROSIS
  • USHER-SYNDROME
  • OPTOGENETIC STIMULATION
  • ADENOASSOCIATED VIRUS
  • VESTIBULAR FUNCTION
  • AUDITORY PATHWAY
  • RESCUES HEARING

Cochlear Gene Therapy for Sensorineural Hearing Loss: Current Status and Major Remaining Hurdles for Translational Success

Tools:

Journal Title:

Frontiers in Molecular Neuroscience

Volume:

Volume 11

Publisher:

, Pages 221-221

Type of Work:

Article | Final Publisher PDF

Abstract:

Sensorineural hearing loss (SNHL) affects millions of people. Genetic mutations play a large and direct role in both congenital and late-onset cases of SNHL (e.g., age-dependent hearing loss, ADHL). Although hearing aids can help moderate to severe hearing loss the only effective treatment for deaf patients is the cochlear implant (CI). Gene- and cell-based therapies potentially may preserve or restore hearing with more natural sound perception, since their theoretical frequency resolution power is much higher than that of cochlear implants. These biologically-based interventions also carry the potential to re-establish hearing without the need for implanting any prosthetic device; the convenience and lower financial burden afforded by such biologically-based interventions could potentially benefit far more SNHL patients. Recently major progress has been achieved in preclinical studies of cochlear gene therapy. This review critically evaluates recent advances in the preclinical trials of gene therapies for SNHL and the major remaining challenges for the development and eventual clinical translation of this novel therapy. The cochlea bears many similarities to the eye for translational studies of gene therapies. Experience gained in ocular gene therapy trials, many of which have advanced to clinical phase III, may provide valuable guidance in improving the chance of success for cochlear gene therapy in human trials. A discussion on potential implications of translational knowledge gleaned from large numbers of advanced clinical trials of ocular gene therapy is therefore included.

Copyright information:

© 2018 Zhang, Kim, Wang, Cai, Feng, Kong and Lin.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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