Treating Hearing Loss: From Cochlear Implantation to Gene Therapy.

Area of Science:

• Otolaryngology
• Genetics
• Regenerative Medicine

Background:

• Gene therapy is emerging as a novel treatment for genetic hearing loss.
• Restoration of natural hearing via gene therapy differs from artificial hearing provided by cochlear implantation.
• Mutations in the OTOF gene cause a form of congenital deafness (DFNB9).

Purpose of the Study:

• To review the current state of gene therapy for OTOF-gene mutations.
• To identify knowledge gaps and future directions for gene therapy in hearing loss.
• To compare the efficacy and safety of gene therapy with cochlear implantation.

Main Methods:

• Analysis of published trial data for DFNB9 patients treated with gene therapy.
• Review of adverse events and audibility improvements.
• Identification of areas for future research, including temporal processing and comparative efficacy.

Main Results:

• Gene therapy demonstrated substantial (average 52.4 dB improvement), rapid, and stable hearing restoration in DFNB9 patients.
• Adverse events were predominantly mild (244 Grade I/II), with few severe events (2 Grade III) and no serious adverse events.
• Significant individual variability in outcomes was observed, ranging from normal audibility to severe hearing loss.

Conclusions:

• Gene therapy is a promising treatment for monogenic forms of congenital deafness, particularly OTOF-gene mutations.
• Further research is required to address individual outcome variability, temporal processing, and direct comparisons with cochlear implantation.
• Advancements in delivery and gene editing technologies are expected to enhance the safety and efficacy of gene therapy for hearing loss.