Anti-epileptic drugs may help prevent and treat
noise-induced hearing loss
By Gwen Ericson
Editor: Here's news of an anti-epileptic drug that prevents and
treats noise-induced hearing loss. Because it is already FDA-approved
(although for other applications), this drug could be commercially
available sooner than the brand new drugs.
Here's the press release from the folks at Washington University,
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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(r)) or ethosuximide (Zarontin(r))
- 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.
