Gene therapy for the inner ear

Abstract

Animal studies on inner ear development, repair and regeneration provide understanding of molecular pathways that can be harnessed for treating inner ear disease. Use of transgenic mouse technology, in particular, has contributed knowledge of genes that regulate development of hair cells and innervation, and of molecular players that can induce regeneration, but this technology is not applicable for human treatment, for practical and ethical reasons. Therefore other means for influencing gene expression in the inner ear are needed. We describe several gene vectors useful for inner ear gene therapy and the practical aspects of introducing these vectors into the ear. We then review the progress toward using gene transfer for therapies in both auditory and balance systems, and discuss the technological milestones needed to advance to clinical application of these methods.

Fig. 1

A schematic diagram showing the left inner ear (a), the major cell types that typically require gene transfer for research or clinical purposes (b) and the most efficient ways to transduce mesothelial cells (c) and supporting cells (d). (a) Microtubes (yellow) inserted into the scala tympani via a cochleostomy (left), or through the round window (middle) or via a canalostomy (right) for delivering therapeutic agents to the mature left inner ear. (b) A cross section through the membranous labyrinth and surrounding tissues showing the three fluid chambers (scala vestibule, SV; scala tympani, ST; and scala media, SM; and specific cell types: inner hair cells (IHCs), outer hair cells (OHCs), supporting cells (SCs) and spiral ganglion neurons (SGNs) in Rosenthal’s canal. (c) Vectors carrying transgenes inserted via ST usually transduce the mesothelial cells. (d) When transgene vectors are inoculated into the SM, supporting cells are usually transduced.