BME PhD Proposal Seminar: Miriam Gladstone

Development of Therapeutic Strategies for the Treatment of Hearing Loss and Deafness

Supervised by Dr. Robert Frisina & Dr. David Borkholder

Abstract

Based on statistics from the NIDCD (National Institute on Deafness and Other Communication Disorders) more than 17% of US adults have some form of hearing loss. This percentage increases with age such that at least 47% of adults over the age of 75 have a hearing deficit. In order to develop effective therapies for the cochlea, multiple parameters of the infusion / surgical paradigm must first be established. Computer modeling of biological systems can be an invaluable tool for accomplishing this task, as quantities such as the concentration of the therapeutic agent, volume and flow rate of the infusate, and which delivery system leads to the optimal concentration profile are all parameters that can be investigated with a biologically accurate fluid dynamic model of the inner ear. My overall goal is to further develop therapeutic strategies for the treatment of hearing loss and deafness by creating a computational model of the inner ear that can describe both the young adult and aged auditory system. We will validate this model with in vivo experiments using mice as our animal model.

A computational model will be developed in Matlab using a combination of classic fluid dynamics and electric circuit theory. In addition, we will be able to directly measure transport and clearance parameters in the system using micro Computed Tomography (microCT) in an innovative way to monitor the distribution of contrast agent throughout the fluid spaces of the cochlea in real time. The model will be validated with in vivo experiments involving the infusion of ototoxic agents and simultaneous auditory testing, and will be tested with in vivo experiments subjecting mice to loud noise leading to acoustic injury and administering antioxidant agents which have been shown to have protective affects against noise damage.

Together, these findings will increase our understanding of the distribution of exogenous agents when applied to the inner ear. This work will provide information that can lead to translational research and clinical development of therapeutic strategies to preserve hearing, or correct or prevent hearing loss. Our work will allow for the characterization of concentration profiles throughout the fluid spaces of the cochlea and consequently should be applicable to multiple therapeutic strategies involving directed delivery of therapeutic agents to the inner ear.