Active Research

Principal Investigator: Dennis Trune, Ph.D., Steven Hefeneider, Ph.D.

Objective: To characterize the steroid-driven cellular and molecular processes with steroid treatments that functionally isolate the receptors and measure changes in the cochlear homeostatic and inflammatory gene expression they control.

Background: Corticosteroids remain the only proven first-line therapeutic treatment for many forms of hearing loss. However, we currently have little understanding of what cochlear physiologic and metabolic processes respond to steroids and therefore are relevant to hearing recovery.  As a result, we do not know why steroids are effective in some forms of hearing loss and not others. Therefore, it is imperative for improved treatment of hearing loss to better understand the cellular and molecular processes in the ear that are impacted by systemic or middle ear steroid delivery.

Findings: Combination steroid treatment with both the glucocorticoid and mineralocorticoid was effective at doses lower than the effective dose of either alone, suggesting an additive or interactive effect when they are combined. Combination therapy may be feasible at doses low enough to avoid the severe side effects of glucocorticoids that currently prevent long-term management. Treatment of mice with the commercially available mineralocorticoid fludrocortisone was as effective as the natural mineralocorticoid aldosterone in preventing hearing loss. Studies also indicate that the glucocorticoids given for inner ear disease may bind to the mineralocorticoid receptor to improve cochlear ion homeostasis and hearing. Also, the intratympanic delivery of steroids for hearing loss will deliver steroids into the inner ear quickly, but levels decline by 24 hours.