Development of atonal therapy for bilateral vestibular hypofunction

University Of Kansas Medical Center, Kansas City KS

Investigators

Linked publications & trials

Abstract

[unreadable] DESCRIPTION (provided by applicant): Balance disorders affect a large proportion of the population resulting in an estimated 5 million physician visits a year in the U.S. (National Ambulatory Medical Care Survey 1991). Although there are a diverse series of underlying etiologies for balance disorders, loss of vestibular hair cells represents a common cause of balance dysfunction. Other than rehabilitation there are no directed therapies aimed at recovery of vestibular function. This series of studies aims to develop a molecular solution for bilateral vestbibular hypofunction (BVH). The success of a molecular therapy program for inner ear disease depends on our ability to correctly target a patient population. Severe BVH results in permanent chronic balance dysfunction and oscillopsia. To date there is no prosthetic device such as a hearing aid or cochlear implant for loss of vestibular function. Recovery from vestibular loss may only be possible through replacement of the missing vestibular sensory cells. Patients with bilateral vestibular disorders, represent a critical patient population in need of a therapeutic approach for whom no other clinical treatment is available. Vestibular hypofunction due to aminoglycoside toxicity represents a disorder where we understand the pathology, facilitating the design of rational pharmacotherapy. Several independent studies have established that delivery of the atonal 1 gene can result in the generation of hair cells. The proposed grant aims to advance this proof of concept to the clinic. The proposed studies will refine a clinical lead molecule based on the delivery of the human homolg of atoh1, Hath1. We will select a lead molecule, determine the lead molecule therapeutic index, generate a GMP manufactured product and conduct toxicology studies and to draft an IND for a proposed human phase 1 clinical trial for aminoglycoside induced bilateral vestibular hypofunction. This proposal aims to translate recent key findings from gene research into a therapy for patients with an unmet medical need. Balance disorders affect a large proportion of the population and there are little or no current therapies to address these severe conditions. The gene controlling development of hearing and balance sensory cells will be tested for its ability to restore balance function in models that prepare moving this molecular therapeutic into clinical studies. [unreadable] [unreadable] [unreadable] [unreadable]