Prevention of Noise-Induced Hearing Loss: Potential Therapeutic Agents

Abstract

Noise-induced hearing loss (NIHL) is a significant clinical, social, and economic issue. The development of novel therapeutic agents to reduce NIHL would increase the potential protection of workers exposed to occupational noise, as well as noise-exposed military populations. Adolescents and young adults may perhaps benefit as well. A better understanding of oxidative stress during and after noise, and activation of other mechanisms of cellular and molecular events that lead to cell death subsequent to noise insult, has advanced the potential to identify and develop novel therapeutic agents. Identification of oxidative stress and improved knowledge as to how cells die has been particularly significant for the development of novel therapeutic agents to reduce NIHL. Widespread clinical acceptance of any novel ­therapeutic will be driven by demonstration that the agent reduces permanent noise-induced threshold shift (PTS) in randomized, placebo-controlled, prospective human clinical trials. Identification and access to populations that develop PTS despite the use of traditional hearing protection devices (which are ethically required in such studies) is challenging. Moreover, such studies are necessarily slow, ­requiring years of data collection from each individual subject, given that NIHL is generally slow to develop. Given these and other obstacles, many groups are ­turning to temporary threshold shift (TTS) models for initial human proof of concept ­testing. Thus, the relationship between PTS and TTS, and the clinical relevance of TTS deficits, are reviewed first.