Anti-epileptic drugs may help prevent and treat noise-induced hearing loss

On the battlefield, a soldier’s hearing can be permanently damaged in an instant by the boom of an explosion, and thousands of soldiers returning from Iraq have some permanent hearing loss. But what if soldiers could take a pill before going on duty that would prevent damage to hearing?

Research at Washington University School of Medicine in St. Louis suggests a medicinal form of hearing protection may someday be a possibility. A group headed by Jianxin Bao, Ph.D., research associate professor of otolaryngology and head of the Central Institute for the Deaf’s Presbycusis and Aging Laboratory, has found that two anti-epileptic drugs can prevent permanent hearing loss to a significant degree in mice exposed to loud noises.

“The military has a tremendous need for preventing noise-induced hearing loss,” Bao says. “But others would also benefit. For example, many hunters have hearing loss on the side where they hold their gun, and pilots are especially prone to hearing loss because of the noise in airplane cabins. Protective equipment or earplugs aren’t always appropriate, and right now no drug on the market can prevent or treat noise-induced hearing loss.”

Bao’s laboratory is dedicated to the study of both age-related and noise-induced hearing loss. About 28 million Americans have a hearing impairment, and excessive noise is the predominant cause of permanent hearing loss. At least 30 million people in the United States encounter hazardous levels of noise at work, particularly in jobs such as construction, mining, agriculture, manufacturing, transportation and the military.

Bao and colleagues found that if they exposed mice to loud sounds and then gave them trimethadione (Tridione®) or ethosuximide (Zarontin®) — anticonvulsive medications used to treat epilepsy — they could prevent a significant amount of permanent hearing loss. When mice got the medications before noise exposure, only trimethadione, not ethosuximide, significantly reduced subsequent hearing loss. The results are reported in Hearing Research and are now available through advanced online publication.

Bao notes that other researchers are investigating agents such as antioxidants for their potential in preventing hearing loss, but the two anticonvulsive drugs his lab studied have had FDA approval and so could be used much sooner in clinical trials that study hearing loss.

The experiments in mice showed that the drugs could reduce by about five decibels the permanent threshold shift that can occur after noise exposure. For example, if the softest sound the mice could hear before the noise was 30 decibels, after the noise it might take a louder, 50-decibel sound for the untreated mice to hear but only 45 decibels for the treated mice. A decibel is a standard unit of sound, and normal conversation is around 60 decibels.

“In people, a five decibel difference in hearing ability can be important for everyday speech,” Bao says. “We will continue our investigations of these kinds of drugs to see if we can improve the results. One possibility is to combine an anticonvulsant with an antioxidant to increase the protective effect.”

Both drugs tested are T-type calcium channel blockers, which inhibit the movement of calcium ions into nerve cells. In the ear, calcium may play a role in causing damage to hair cells (specialized cells that sense sound vibrations) and the nerve cells that connect the hair cells to the hearing centers of the brain.

These anti-epileptic drugs can have unwanted side effects such as dizziness and sleepiness. “The drugs’ side effects would be detrimental in certain situations,” Bao says. “But lowering the dosage and combining them with other drugs may be effective. Newer versions of anti-epilepsy drugs have fewer side effects, and it may be possible to modify the structure of the drugs so that they don’t cross into the brain, which could avert some side effects.”

Shen H, Zhang B, Shin J-H, Lei D, Du Y, Gao X, Wang Q, Ohlemiller KK, Piccirillo J, Bao J. Prophylactic and therapeutic functions of T-type calcium blockers against noise-induced hearing loss. Hearing Research Dec 31, 2006 (advanced online publication).

Funding from the National Institutes of Health and the National Organization for Hearing Research Foundation supported this research.

Washington University School of Medicine’s full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked fourth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.