Development of dual-action topical therapeutics for cytomegalovirus-induced hearing loss

Statement of Purpose: Statistics suggest that CMV infection is the leading nongenetic cause of hearing loss in children in the United States and the cost associated with diagnosis and treatment of CMV infection has been estimated at $4 billion/year. As a result, several states have mandated healthcare providers to communicate the dangers of congenital CMV infection to pregnant women, and to conduct CMV screening for infants who fail their newborn hearing screening. Existing treatment options employ antivirals such as valganciclovir and primarily target CMV infected infants with severe disease (symptomatic CMV). However, enthusiasm for antiviral agents has been muted due to very modest short-term improvements, uncertain long-term outcomes, reports of adverse effects such as neutropenia (abnormally low levels of neutrophils) and concerns for impaired fertility and teratogenesis. In parallel, a major challenge is the lack of treatment for CMV infected children with initial normal hearing (asymptomatic CMV) who will develop hearing loss later in life. In the context of universal CMV screening, treating every asymptomatic CMV infected child with an antiviral would subject the majority of these children to the risks of antiviral therapy without any benefit to their hearing outcomes since 90% would not be expected to develop hearing loss. Therefore, there is an urgent need to develop alternate therapeutics that will provide better prophylaxis and treatment options for CMV-infected neonates. Our approach is to use hyaluronic acid (HA), which was shown to have intrinsic anti-inflammatory properties and to enhance drug transmembrane permeation, as a carrier for antioxidants into the inner ear.