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Interdisciplinary Initiatives Program Seed Grant: Materials and Methods for Sustained Delivery of Drugs and Genes to the Cochlea

Seed Grants
Awarded in 2018

Interdisciplinary Initiatives Program Round 9 - 2018

Eric Appel, Materials Science & Engineering
Anthony Ricci, Otolaryngology

Our goal is to develop a transformational treatment strategy for inner ear diseases where repeated dosing is not possible or highly risky. Sensorineural hearing loss (SNHL) is the most common sensory deficit in humans, with an estimated prevalence of over 300 million individuals worldwide. SNHL occurs at the level of the peripheral auditory system, through degenerative mechanisms that damage the cochlea’s sensory epithelium, namely the inner and outer hair cells and the spiral ganglion neurons. Increased rates of hearing loss are associated with aging, prolonged exposure to noise or ototoxic drugs, Meniere’s disease, and genetic mutations. Military service is also a risk factor, where the incidence of noise induced hearing loss is nearly 30 per 100 person-years, for which the Veterans Administration pays over $1B annually in compensation. Pharmacological therapies for hearing loss are being developed, and include small molecules, peptides, proteins, and gene vectors. Yet, the cochlea of the inner ear represents one of the only remaining organs inaccessible to surgical or chemical therapeutic strategies. A promising delivery approach for inner ear applications is intracochlear delivery; however, rapid clearance and diffusion-limited transport along the tortuous fluid compartments in the cochlea leads to (i) short duration of therapy after intracochlear injection, and (ii) a poor distribution of drug along the cochlea’s sensory epithelium. The clinical viability of intracochlear delivery relies on the development of a delivery vehicle that controls and prolongs release to achieve a uniform distribution of drug along the cochlear axis. To address this unmet clinical need, we have put together an interdisciplinary team to develop both a new surgical approach and a new sustained drug delivery platform that can enable safe and efficacious strategies for prolonged treatment inner ear diseases following a single administration. By bringing together technology, expertise, and approaches from disparate disciplines spanning materials science, bioengineering, molecular & cellular physiology, and otolaryngology we will catalyze the development of transformational therapies for inner ear diseases. We will use animal models of acoustic injury and congenital deafness to validate the ability of this novel therapeutic approach. Aside from the scientific advances, this project will support the development of a new, interdisciplinary training environment that will allow trainees to draw on the diverse expertise, resources and perspectives of the labs involved in this project.