title: The Sustained-Exposure Dexamethasone Formulation OTO-104 Offers Effective Protection against Noise-Induced Hearing Loss.
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.
authors.affiliation: Otonomy Inc., San Diego, Calif., USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Harrop-Jones
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wang
authors.forename: Rayne
authors.initials: R
authors.lastname: Fernandez
authors.forename: Luis
authors.initials: L
authors.lastname: Dellamary
authors.forename: Allen F
authors.initials: AF
authors.lastname: Ryan
authors.forename: Carl
authors.initials: C
authors.lastname: LeBel
authors.forename: Fabrice
authors.initials: F
authors.lastname: Piu
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006168:Guinea Pigs; D006309:Hearing / Q000187:drug effects*; D006317:Hearing Loss, Noise-Induced / Q000517:prevention & control*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D000069555:Injection, Intratympanic; D020442:Poloxamer
chemical_list: D005938:Glucocorticoids; D020442:Poloxamer; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C004180:dexamethasone 21-phosphate; D003907:Dexamethasone