Current Status and Prospects of Gene Therapy for the Inner Ear

Abstract

Inner ear diseases are common and often result in hearing disability. Sensorineural hearing loss is the main cause of hearing disability. So far, no effective treatment is available although some patients may benefit from a hearing aid equipped with a hearing amplifier or from cochlear implantation. Inner ear gene therapy has become an emerging field of study for the treatment of hearing disability. Numerous new discoveries and tremendous advances have been made in inner ear gene therapy including gene vectors, routes of administration, and therapeutic genes and targets. Gene therapy may become a treatment option for inner ear diseases in the near future. In this review, we summarize the current state of inner ear gene therapy including gene vectors, delivery routes, and therapeutic genes and targets by examining and analyzing publications on inner ear gene therapy from the literature and patent documents, and identify promising patents, novel techniques, and vital research projects. We also discuss the progress and prospects of inner ear gene therapy, the advances and shortcomings, with possible solutions in this field of research.

New treatment options for hearing loss

“…Successes in gene therapy for disease in other organs, such as the retina 133 , have suggested plausible therapeutic strategies that can be applied to the inner ear. Gene therapy is unlikely to be as widely applicable to hearing loss as a viable hair cell-regeneration strategy would be, but nonetheless, it may be very effective in some cases 134,135 .…”

“…138). Correcting genetic defects in human embryos using similar in utero techniques may someday prove viable 135 , although technical and ethical issues are considerable.…”

Ultrasound-induced microbubble cavitation via a transcanal or transcranial approach facilitates inner ear drug delivery

“…Some agents such as collagenase (6), histamine and local anesthetic phenols (7), and hyaluronic acid (8) have been applied to the RWM to destroy its outer epithelial cells and thereby enhance drug delivery without resorting to surgery. However, these approaches may cause infection in the middle ear cavity and damage the RWM -or even the inner ear, itself (9).…”

Treatment of autosomal dominant hearing loss by in vivo delivery of genome editing agents

“…Complementation of wild-type alleles, or silencing dominant negative mutant alleles, have shown promising results in animal models 6, 7 . Nonetheless, current approaches face potential challenges including immunogenicity, oncogenicity, and limitations of viral vectors 8,9 .…”