Concepedia

The Sustained-Exposure Dexamethasone Formulation OTO-104 Offers Effective Protection against Noise-Induced Hearing Loss

Anne Harrop-Jones, Xiaobo Wang, Rayne Fernandez, Luis Dellamary, Allen F. Ryan, Carl LeBel, Fabrice Piu

Audiology and Neurotology · 2015 · 31 citations · 25 references

TL;DR

The study investigated the otoprotective effects of OTO‑104 administered before and after acute acoustic trauma. The authors used a single intratympanic injection of OTO‑104 in guinea pigs and showed that otoprotection requires activation of classical glucocorticoid and mineralocorticoid receptor pathways. Doses of at least 2.0 % OTO‑104 significantly protected against noise‑induced hearing loss when given 1 day before or up to 3 days after trauma, remained effective at higher trauma levels, and outperformed dexamethasone sodium phosphate and standard steroid solutions.

Abstract

The otoprotective effects of OTO-104 were investigated both prior to and following acute acoustic trauma. Guinea pigs received a single intratympanic injection of OTO-104 and were assessed in a model of acute acoustic trauma. Doses of at least 2.0% OTO-104 offered significant protection against hearing loss induced by noise exposure when administered 1 day prior to trauma and up to 3 days thereafter. Otoprotection remained effective even with higher degrees of trauma. In contrast, the administration of a dexamethasone sodium phosphate solution did not protect against noise-induced hearing loss. Activation of the classical nuclear glucocorticoid and mineralocorticoid receptor pathways was required for otoprotection by OTO-104. The sustained exposure properties of OTO-104 were also superior to a steroid solution.