Development of gene therapy for inner ear disease: Using bilateral vestibular hypofunction as a vehicle for translational research

Despite the significant impact of hearing and balance disorders on the general population there are currently no dedicated pharmaceuticals that target the inner ear. Advances in molecular biology and neuroscience have improved our understanding of the inner ear allowing the development of a range of molecular targets that have the potential to treat both hearing and balance disorders. One of the principal advantages of the inner ear is that it is accessible through a variety of approaches that would allow a potential to be delivered locally rather than systemically. This significantly broadens the potential medications that can be developed and opens the possibility of local gene delivery as a therapeutic intervention. Several potential clinical targets have been identified including delivery of neurotrophin expressing genes as an adjunct to cochlear implantation, delivery of protective genes to prevent trauma and the development of strategies for regenerating inner ear sensory cells. In order to translate these potential therapeutics into humans we will want to optimize the gene delivery methodology, dosing and activity of the drug for therapeutic value. To this end we have developed a series of adenovectors that efficiently transduce the inner ear. The use of these gene delivery approaches are attractive for the potential of hair cell regeneration after loss induced by trauma or ototoxins. This approach is particularly suited for the development of molecular therapies targeted at the vestibular system given that no device based therapeutic such a cochlear implant available for vestibular loss.

► Delivery of atoh1 to the inner ear via gene therapy has the potential to regenerate hair cells.
► Supporting cell specific promoters and targeting of vectors has the potential to improve the efficiency of atonal gene therapy.
► Adenovectors provide a delivery platform that is well suited for use in the inner ear.