Development of Ebselen, a Glutathione Peroxidase Mimic, for the Prevention and Treatment of Noise-Induced Hearing Loss
The development of therapeutics for the prevention and treatment of sensorineural hearing loss remains an elusive goal for auditory scientists and clinicians worldwide. While much research has focused on the histopathology associated with exposure to intense noise or ototoxins (i.e., loss of hair cells), the biochemical and genetic mechanisms that evoke or mediate hair cell death and dysfunction are still under investigation and debate. Many have observed an early oxidative burst in the cochlea that leads to an increase in lipoperoxidation and the activation of cell death pathways, ultimately resulting in apoptosis. In support of this hypothesis, many have protected the cochlea and preserved auditory function by injecting high doses of antioxidants or inhibitors of cell death activation prior to intense noise or ototoxin exposure. Here we discuss a compound currently in Phase II clinical testing for the prevention and treatment of noise-induced hearing loss. This article will review the historic background and pertinent preclinical and clinical data available for ebselen, a novel drug that mimics the activity of glutathione peroxidase, a catalytic antioxidant enzyme that is essential for the peripheral auditory system.
from Seminars in Hearing