Cochlear protein biomarkers as potential sites for targeted inner ear drug delivery

James G Naples,Andrew Ramsey,Lauren E Miller,Daqing Li

doi:10.1007/s13346-019-00692-5

Abstract

The delivery of therapies to the cochlea is notoriously challenging. It is an organ protected by a number of barriers that need to be overcome in the drug delivery process. Additionally, there are multiple sites of possible damage within the cochlea. Despite the many potential sites of damage, acquired otologic insults preferentially damage a single location. While progress has been made in techniques for inner ear drug delivery, the current techniques remain non-specific and our ability to deliver therapies in a cell-specific manner are limited. Fortunately, there are proteins specific to various cell-types within the cochlea (e.g., hair cells, spiral ganglion cells, stria vascularis) that function as biomarkers of site-specific damage. These protein biomarkers have potential to serve as targets for cell-specific inner ear drug delivery. In this manuscript, we review the concept of biomarkers and targeted- inner ear drug delivery and the well-characterized protein biomarkers within each of the locations of interest within the cochlea. Our review will focus on targeted drug delivery in the setting of acquired otologic insults (e.g., ototoxicity, noise-induce hearing loss). The goal is not to discuss therapies to treat acquired otologic insults, rather, to establish potential concepts of how to deliver therapies in a targeted, cell-specific manner. Based on our review, it is clear that future of inner ear drug delivery is a discipline filled with potential that will require collaborative efforts among clinicians and scientists to optimize treatment of otologic insults.Graphical

Highlights

The cochlea is a privileged organ within the temporal bone that is protected from the external environment by the otic capsule bone, the round window membrane (RWM), and bloodlabyrinth barrier
Unlike many of the other cochlear biomarkers, prestin is specific to the OHCs and does not exist within any other cell type within the cochlea [25]
There are a wide range of cochlear insults that present with permanent sensorineural hearing loss (SNHL), tinnitus, and/or vertigo

Summary

Introduction

The cochlea is a privileged organ within the temporal bone that is protected from the external environment by the otic capsule bone, the round window membrane (RWM), and bloodlabyrinth barrier. Small changes within the local environment of the cochlea can introduce acquired insults, which present as a sensorineural hearing loss (SNHL) in the clinical setting and can be accompanied by tinnitus and vertigo. These characteristics introduce significant challenges when treating acquired cochlear disorders. There are various well-established etiologies of acquired cochlear insult that include excessive noise exposure, ototoxic medications, and idiopathic causes such as Meniere’s disease and sudden SNHL While each of these various etiologies produces a similar clinical effect of SNHL, there is evidence to suggest that many of the causes of acquired SNHL preferentially introduce insults to specific locations within the cochlea (inner hair cells (IHC) [1], outer hair cells (OHC) [2], stria vascularis (SV) [3], spiral ganglion neurons (SG) [4], and supporting cells [5]). Clinical and basic science research has led to early foundational understandings of the various mechanisms by which therapies can penetrate the protective barriers and reach locations within the cochlea

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