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.