Hearing is restored in deaf mammals

Michigan scientists use gene therapy to form cells in guinea pigs' ears

February 14, 2005|By Thomas H. Maugh II | Thomas H. Maugh II,LOS ANGELES TIMES

Michigan researchers have restored hearing in deaf mammals for the first time, a feat that represents a major step toward the treatment of the 27 million Americans with acquired hearing loss.

By inserting a corrective gene with a virus, the team induced the formation of new cochlear hair cells - key intermediates in converting sound waves into electrical impulses - in the ears of artificially deafened adult guinea pigs.

They later demonstrated that the animals responded to sounds, according to the study published today in the journal Nature Medicine.

"A lot of the techniques would fairly easily translate into a clinical setting" for use in humans, said neuroscientist Matthew W. Kelley of the National Institute on Deafness and Other Communication Disorders, who was not involved in the research.

Humans have about 16,000 hair cells in the cochlea of each ear, where they convert sound waves into nerve impulses. The cells are easily damaged by loud noises, aging, infections and certain medications. Once damaged, they cannot regenerate on their own.

The key to the generation of new hair cells is a gene called Atoh1, discovered in fruit flies in 1998 by geneticist Huda Y. Zoghbi of the Baylor College of Medicine. Variants of the gene have since been discovered in almost all species of animals.

During fetal development, the gene converts some cells in the ear into hair cells. In other ear cells, called supporting cells, its activity is suppressed.

Researchers showed that, working in laboratory dishes, the gene could convert supporting cells into hair cells.

Two years ago, Yehoash Raphael and Kohei Kawamoto of the University of Michigan Medical School reported that inserting the gene into supporting cells in guinea pigs produced thousands of new hair cells.

"Everybody in the field was amazed this worked," Kelley said. "We thought it was going to be really hard and that it would require a whole lot of genes."

But in those experiments, the researchers did not deafen the animals first. This time they did, using chemicals to kill the hair cells in both ears of 10 guinea pigs. Microscopic images taken three days later confirmed that all the cells had been destroyed.

On the fourth day, they used gene therapy with a viral vector to insert the Atoh1 gene into the guinea pigs' left ears. Within two months, new hair cells had appeared in the treated ears but not in the untreated right ears.

The team tested brainstem response to measure the guinea pigs' ability to hear. In effect, they observed increases in brain activity when they exposed the animals to noises.

"The bottom line is, their hearing gets better, and that is a very big step," Kelley said.

Raphael and his colleagues are trying to determine how good the restored hearing is, whether the animals can differentiate between loud and soft, and between different frequencies. They are also studying animals deafened by other means, older animals and animals that have been deaf longer.

Even if the experiments are successful, it will be years before the technique can be tried in humans, experts said.

The Los Angeles Times is a Tribune Publishing newspaper.

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