Targeting the cochlear power house to treat hearing loss

Sensory hair cells and auditory neurons within the inner ear’s cochlea have been the main cellular targets for gene therapy in age-related hearing loss.

However, we revealed that other cell types located in the stria vascularis, a structure in the edge of the cochlea responsible for the electric potential required for mechanotransduction. Dysfunctions in the stria vascularis can cause profound hearing loss.

We have recently uncovered a new route to deliver gene therapy in the cochlea without performing invasive inner ear surgeries. We evidenced that cerebrospinal fluids (CSF) reach the cochlea.

Adeno-associated viruses (AAVs) can reach the cochlea via the CSF and transduce cells of interest and fully restore hearing in an adult mouse model of human deafness.

Here we will use this delivery route to screen for AAV serotypes that can target cells from the stria vascularis, without transducing other cochlear cell types, nor other vital organs. We will then treat various models of deafness where specific cell types of the stria vascularis are affected.

Finally, we will use single-cell RNA sequencing to verify that the cellular composition in the cochlea and their transcriptome is unaltered.

Given the increasing use of AAVs to treat hearing loss, this project will generate fundamental knowledge for the treatment of various forms of hearing loss, the prevalence of which is predicted to reach 2.4 billion in 2050, and has become a major public health concern.