Diagnostic and therapeutic applications of genomic medicine in progressive, late-onset, nonsyndromic sensorineural hearing loss

Joaquin E. Jimenez, Aida Nourbakhsh, Brett Colbert, Rahul Mittal, Denise Yan, Carlos L. Green, Eric Nisenbaum, George Liu, Nicole Bencie, Jason Rudman, Susan H. Blanton, Xue Zhong Liu

Research output: Contribution to journalReview articlepeer-review

Abstract

The progressive, late-onset, nonsyndromic, sensorineural hearing loss (PNSHL) is the most common cause of sensory impairment globally, with presbycusis affecting greater than a third of individuals over the age of 65. The etiology underlying PNSHL include presbycusis, noise-induced hearing loss, drug ototoxicity, and delayed-onset autosomal dominant hearing loss (AD PNSHL). The objective of this article is to discuss the potential diagnostic and therapeutic applications of genomic medicine in PNSHL. Genomic factors contribute greatly to PNSHL. The heritability of presbycusis ranges from 25 to 75%. Current therapies for PNSHL range from sound amplification to cochlear implantation (CI). PNSHL is an excellent candidate for genomic medicine approaches as it is common, has well-described pathophysiology, has a wide time window for treatment, and is amenable to local gene therapy by currently utilized procedural approaches. AD PNSHL is especially suited to genomic medicine approaches that can disrupt the expression of an aberrant protein product. Gene therapy is emerging as a potential therapeutic strategy for the treatment of PNSHL. Viral gene delivery approaches have demonstrated promising results in human clinical trials for two inherited causes of blindness and are being used for PNSHL in animal models and a human trial. Non-viral gene therapy approaches are useful in situations where a transient biologic effect is needed or for delivery of genome editing reagents (such as CRISPR/Cas9) into the inner ear. Many gene therapy modalities that have proven efficacious in animal trials have potential to delay or prevent PNSHL in humans. The development of new treatment modalities for PNSHL will lead to improved quality of life of many affected individuals and their families.

Original languageEnglish (US)
Article number144677
JournalGene
Volume747
DOIs
StatePublished - Jul 15 2020
Externally publishedYes

Keywords

  • Autosomal dominant hearing loss
  • Gene therapy
  • Genomic medicine
  • Noise induced hearing loss
  • Ototoxicity
  • Presbycusis

ASJC Scopus subject areas

  • Genetics

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