Minimally Invasive Delivery System for Treatment of Inner Ear Disorders

PROJECT SUMMARY PROBLEM Hearing loss is the most common sensory disorder in human populations across the globe affecting an estimated million people in the United States and million people worldwide As a primary means of interpersonal communication hearing is central to daily life and its loss can have dramatic impact on cognitive development in children mental health in adolescents and adults contribute to dementia in the elderly and can result in an overall increase in mortality There are currently no drugs approved for the treatment of hearing loss caused by damage to the sensory cells of the cochlea or to the auditory nerve sensorineural hearing loss A major barrier to the development and evaluation of promising new therapies is the inability to deliver macromolecules or complex regimen of small molecules to the sensory cells of the cochlea NEED There is a pressing need for a delivery system that can safely and reliably distribute a range of therapeutic modalities to the sensory epithelium along the length of the cochlea GOAL The goal of the proposed studies is to develop a novel cochlear delivery system and quantify its distribution and safety profile in a large animal model COMPANY S TECHNOLOGY PRELIMINARY DATA Akouos is building off of a decade of work studying drug distribution in the cochlea This work has informed key design parameters of a robust delivery system including infusion volumes and flow rates that can be safely tolerated and have uncovered unanticipated barriers to broad distribution in vivo Based on these prior studies we have designed and built an acute delivery system capable of delivering a wide range of molecules including macromolecules and nanoparticles directly to the cochlea via the round window membrane AIMS Here we propose studies to refine key device parameters and a surgical procedure for application in a sheep model that closely resembles human middle and inner ear anatomy Further we propose a distribution and safety study of the delivery system to demonstrate effective distribution of adeno associated virus AAV particles along the basal apical axis of the cochlea in the sheep model The proposed project will demonstrate that an acute delivery system can safely and reliably deliver macromolecules throughout the cochlea and thereby provide a means to test novel therapies that have the potential to prevent and reverse hearing loss due to multiple causes MILESTONE A delivery system that can distribute AAV particles to achieve transgene expression that differs no more than from cochlear base to apex in a large animal model without significantly increasing hearing thresholds WHAT S NEXT At the successful conclusion of this Phase I SBIR we will be poised to move forward into IND enabling studies with a gene therapy candidate to support human clinical trials for a form of monogenic deafness Phase II of the SBIR proposal will fund a confirmation proof of concept study in a transgenic disease model as well as a GLP toxicity study in a large animal model Project Narrative Hearing loss is a major unmet need with profound impact on individual well being the public health and the global economy A principal reason for the lack of hearing loss therapies is that the sensory cells of the inner ear are bathed in a fixed volume fluid encased in a bony labyrinth and buried within the temporal bone of the skull representing a significant drug delivery challenge that has impeded evaluation and development of potential therapies especially those of great promise that are protein or nucleic acid based Akouos aims to address this challenge by developing a novel delivery system that can simply and safely deliver a wide range of therapeutic modalities to sensory cells throughout the inner ear and thereby enable the development of new drugs for patients suffering from hearing loss