[RESEARCH] David Bakhos, Winner of the call for projects from Fondation pour l'Audition

Abstract

The controlled, targeted delivery of therapeutic agents to the inner ear represents a challenge for management of patients with sensorineural hearing loss. At present, these agents are delivered mainly by the systemic or trans-tympanic route. The systemic route does not enable targeted delivery to the inner ear. While trans-tympanic injection avoids many of the undesirable side effects associated with systemic delivery, it does not allow for controlled diffusion in the cochlea and part of the injected therapeutic is eliminated from the middle ear via the auditory tube. We propose to use sonoporation to deliver therapeutics to the inner ear at the level of the round window in a sheep model. Our preliminary studies with sonoporation in sheep are encouraging. The overall aim is to demonstrate superior diffusion in the inner ear with sonoporation compared to transtympanic injection in a sheep model. Three steps will be necessary: 1) Demonstrate better diffusion using “loaded” microbubbles (gadolinium-infused), compared to “unloaded” microbubbles (gadolinium in the mixture of microbubbles). 2) Design, fabricate, and bench-test a custom ultrasound probe for sonoporation of the inner ear in sheep. 3) Using the custom probe, compare the diffusion of gadolinium within the cochlea between the sonoporation and trans-tympanic approaches; diffusion will be estimated using MRI. The study will enable us to demonstrate diffusion along the cochlea in a targeted and controlled manner via sonoporation without ototoxicity.
 

Research groups

David Bakhos & Jean-Michel Escoffre
Inserm UMR 1253, iBraiN, Université de Tours
Morphofunctional imaging and therapeutic ultrasound

Cédric Chauvierre
Inserm UMR 1148, LVTS, Université Paris Cité
Cardiovascular bioengineering