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Auditory Achilles' heel
HHIssues
post Sun Jan 22, 2006, 07:30 AM
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source: bhNEWS

The Los Angeles Times, January 16, 2006
--------------------

IN THE LAB

Auditory Achilles' heel

Most hearing loss is due to damaged inner-ear hair cells, so scientists are exploring ways to boost their growth. Success could help fight deafness.

By Linda Marsa, Special to The Times

OVER the years, our ears take a beating. They're assaulted with thunderous music, shrill sirens, blaring TV shows and the incessant background thrum of modern life. Little wonder that by middle age, millions of Americans suffer some degree of hearing loss, mostly due to the cumulative destruction of the delicate sound-sensing cells inside our ear from all this noise.

Once these cells die, they're gone forever and a hearing aid often lies somewhere down the road. But it may not always be that way.

Recently scientists have made significant strides in regenerating auditory hair cells, as they're called: They've identified a key gene responsible for hair cell formation, figured out how to coax stem cells to become hair cells and — for the first time — restored hearing in a deaf mammal.

Such experimental approaches may eventually be used to treat hearing loss or to generate the sense in people who never had it.

At birth, our two inner ears contain about 30,000 auditory hair cells. When sound enters our ears, vibrating bones cause fluid to swoosh around, and, like miniature tuning forks, these sensitive cells sway in response. Then they send electrical signals to the brain's auditory center, and we perceive those signals as sounds.

But the super-sensitive cells can be damaged by overexposure to loud noise, some antibiotic drugs or simply the wear and tear of normal aging. Such damage is the leading cause of hearing impairment.

"Hair cells are the Achilles heel of the auditory system," says Dr. James F. Battey, director of the National Institute on Deafness and Other Communication Disorders in Bethesda, Md. "If we could regenerate these cells, we could cure deafness."

Last year, scientists at the University of Michigan reported doing something like that — in several guinea pigs, anyhow. The animals, which had been purposely deafened with antibiotics, were treated with a gene called Atoh 1, which is known to orchestrate the development of hair cells in embryos.

The scientists used a gutted cold virus as a microscopic cargo ship to ferry the gene into the inner ear of six guinea pigs. Within a month, the treated animals sprouted new hair cells. After two months, the animals had regained some hearing in the 60- to 70-decibel range, which is the equivalent of being able to hear loud speech.

The Michigan team is now refining this technology. So far, the scientists have been able to regenerate normal versions of just one of the two kinds of hair cells contained in an ear. To make hearing sharper, they must have intact copies of both. "We need to make hearing clearer so you can perceive pitch — otherwise, the hearing is distorted and muddied," says Yehoash Raphael, an otolaryngologist at the University of Michigan in Ann Arbor who conducted the studies.

The team is also aware that it will need safe and efficient gene transport vehicles to deliver the gene to the inner ear of humans. (Raphael predicts that breakthroughs in gene transfer technology will provide such vehicles in the not too distant future.) In addition, he says, "we also need to develop surgical methods for inoculating the inner ear with genes because the access to the inner ear in humans is much more complicated than in guinea pigs."

Other researchers are testing different approaches. In 2002, a Harvard Medical School team headed by otolaryngologist Stefan Heller identified stem cells that reside in the inner ear. The existence of such cells implies that it might be possible to wake them up and coax them into developing into hair cells inside the ears of people with hearing loss, says Heller, who is now at the Stanford University School of Medicine in Palo Alto.

With that in mind, Heller's group is busy screening more than 100,000 drugs in the hope of uncovering compounds to stimulate the growth of auditory hair cells, a discovery that could eventually make treating hearing loss as easy as using ear drops.

"That's the Holy Grail," Heller says. "We have some hints and have isolated some promising candidates, but we don't have the magic bullet yet."

Heller's group is planning experiments with human embryonic stem cells — as would be needed if this strategy is to move from lab animals to humans.

No one expects to cure deafness anytime soon, but scientists are optimistic. "Despite the remarkable complexity of auditory hair cells," says Battey, "the amount and rate of progress in finding ways to stimulate their growth has been substantial."

*

Turn down the volume

Overexposure to loud noise is the primary reason why sensory hair cells become damaged. Noise becomes hazardous when the sound is intense (that of a screaming siren or a crying baby) or when there is repeated, prolonged or cumulative exposure to sound levels higher than 85 decibels (roughly the level of a lawnmower or a motorcycle). More than 20 million Americans are regularly exposed to dangerous levels of sound at their workplace, from jackhammers, amplified music or traffic noise. Noise-induced hearing loss can be prevented by reducing sound levels, moderating the volume on personal listening devices, avoiding high-intensity sound, using ear plugs when operating power tools or heavy machinery or wearing earmuffs to muffle loud noises. For more information, the National Institutes of Health's Wise Ears
campaign offers tips on how to preserve hearing at http://www.nidcd.nih.gov/health/wise/index.asp.
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