Gene therapy for inner ear disease: the next targets

Area of Science:

• Otolaryngology
• Genetics
• Molecular Biology

Background:

• Over 100 monogenetic causes of hearing loss exist.
• Successful otoferlin gene therapy trials highlight potential treatments.
• Gene therapy is a rapidly advancing field for treating genetic disorders.

Purpose of the Study:

• To identify genetic hearing loss disorders treatable with current gene therapy technologies.
• To evaluate the feasibility of gene replacement and gene editing for various genetic hearing loss types.
• To discuss key factors influencing the success of gene therapy for hearing loss.

Main Methods:

• Review of current gene therapy technologies and their applicability to genetic hearing loss.
• Analysis of disease characteristics, including affected cell types, gene size, and incidence.
• Consideration of gene replacement versus gene editing strategies for different genetic mutations.

Main Results:

• Genetic hearing losses with residual targetable cells in postnatal to adult ages are optimal targets.
• Disorders like DFNB8 and certain DFNB1 mutations are potentially treatable with gene therapy.
• Gene replacement for recessive disorders is more feasible currently than gene editing for dominant disorders.

Conclusions:

• Postnatal genetic hearing losses are currently the most promising targets for gene therapy.
• Congenital hearing losses causing severe to profound deafness in utero are not yet treatable.
• Gene replacement for recessive hearing loss is expected to advance before gene editing for dominant forms.