Development of Therapeutics to Protect the Inner Ear: Support from Animal Models

 

Colleen LePrell - colleen@phhp.ufl.edu

Department of Communicative Disorders, University of Florida

Gainesville, FL

 

Kevin Ohlemiller

Central Institute for the Deaf, Washington University

St. Louis, MO

 

David Dolan

Josef Miller

University of Michigan

Ann Arbor, MI

 

Popular version of paper 1aPP9

Presented Monday morning, April 19, 2010

159th ASA Meeting, Baltimore, MD

 

 

Noise-induced hearing loss (NIHL) is a significant clinical, social, and economic issue. Approximately 30 million American workers are exposed to hazardous levels of occupational noise, making noise-induced hearing loss (NIHL) one of the most common occupational diseases and the second most self-reported occupational injury or illness (NIOSH, 2001). Noise trauma presents a staggering problem for the US military as well. Single-year disability costs related to hearing loss exceeded $900M for 2006 (United States Army Center for Health Promotion and Preventive Medicine (USACHPPM), 2007). Hazardous noise exposure and hearing loss in the US military is greater than it has been in more than 30 years. Recreational activities, such as attending loud music performances or loud sporting events, or engaging in target shooting activities or hunting, also result in the potential for significant noise exposure and hearing loss. Recent reports suggest that some 12.5% of US children now have NIHL (based on a sample of 5249 children, ages 6 to 19 years old, see Niskar et al., 2001). Taken together, NIHL is not only a current health issue, it is a growing problem. Thus, it is not surprising that several objectives within the Healthy People 2010 campaign by the U.S. Department of Health include reducing the number of new cases of NIHL.

 

Although we once thought virtually all NIHL was a consequence of mechanical damage to cells in the inner ear, we now know that intense metabolic activity drives the formation of free radicals (short-lived, unstable, highly reactive clusters of atoms) in the inner ear. Free radicals are produced normal cell respiration, when glucose and oxygen are converted to a form of energy that cells can use (adenosine triphospate, or, ATP). During noise exposure, energy demands increase in the inner ear, free radicals are produced at an increased rate, and the accumulation of these free radicals initiates a cascade of intra-cellular events that result in cell death in the inner ear, and permanent hearing loss. Studies in animals have clearly shown that free radicals formed during and after noise importantly contribute to NIHL, and many laboratories have demonstrated that free radical scavengers (antioxidants) reduce NIHL in animal subjects. Several different free radical scavengers, each of which attacks free radical formation in the inner ear a bit differently, are now under development as possible commercial products pending proof of efficacy in human subjects.

 

Our group, including investigators at multiple institutions, has specifically shown that the combination of beta-carotene, vitamins C and E, and magnesium is highly effective in reducing NIHL and sensory cell death in guinea pigs and mice when high-level supplements are given to animal subjects prior to noise exposure. Use of this combination of dietary nutrients to prevent noise-induced deficits in human patients has thus become a clinical research goal. NIH-funded clinical trials to determine the potential for use of these nutrients as an effective intervention against human NIHL are in progress, with study populations in the United States, Sweden, and Spain. Translational investigations are essential to confirm potential utility of these agents in the human inner ear.