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Researchers Link Gene to Form of Deafness

January 13, 2005

WASHINGTON (AP) — Researchers have identified a gene that prevents the regeneration of inner ear cells that are critical to hearing, a discovery experts say is the first step toward finding a way to correct the most common form of deafness among the elderly.

In laboratory mouse studies at Massachusetts General Hospital, researchers found that by eliminating the effects of a single gene they could cause inner ear cells vital to hearing to regrow. The regrowth replaces nerve endings, called hair cells, that are often lost to injury or age.

“Most deafness is caused by the loss of these hair cells,” said Zheng-Yi Chen, leader of the hospital research team. “Now we have the means to regenerate these cells.”

The goal, said Chen, is to learn find a way to turn off this gene in the inner ear of humans, probably with a drug, and allow the regrowth of hair cells.

“That would lead to recovery of hearing,” said Chen. He is senior author of the study appearing this week in the journal Science.

Dr. James F. Battey, director of the National Institute of Deafness and Other Communication Disorders, one of the National Institutes of Health, said the discovery by Chen’s team “is a very important first step toward learning” how to restore hearing in human patients.

The hair cells are a key link in the signal chain that makes hearing possible. The cells line the cochlea, part of the inner ear that sends the sensation of sound to the brain.

Sonic vibrations from the eardrum and bones of the middle ear are relayed to the cochlea where they excite the hair cells. This energy is converted to electrical signals that are carried by nerves to the brain and interpreted as sound.

Humans are born with about 50,000 inner ear hair cells, but the cells decline over time due to injury, disease or age. Once enough of the cells die, then the hearing begins to fade because the cells do not naturally regenerate, said Stefan Heller, a hearing researcher at the Massachusetts Eye and Ear Infirmary.

“Once these cells are lost they are lost for good,” he said. “In profound deafness, you can get down almost zero cells.”

Heller said the study by Chen’s group is exciting to hearing researchers because “it shows for the first time that you can regenerate adult hair cells in the inner ear. If this leads to a drug that will do that, then it could be the cure (for deafness.)”

The inner ear organ that controls balance also uses the hair cells and the gradual loss of these cells leads to balance disorders that are also common among the elderly.

In the study, the research team surveyed all the genes that are active during the embryonic development of the inner ear. The researchers discovered that a protein made by the retinoblastoma, or Rb1, gene halted the growth of hair cells. In effect, they found that the Rb1 protein was a molecular switch that turned off hair cell proliferation.

They then studied a mouse developed by Philip Hinds of the Tufts-New England Medical Center that did not express Rb1 protein in the inner ear. Mice lacking this gene tended to run in circles, suggesting an abnormality in the balance system. Researchers found that the animals had more hair cells in their inner ears than did mice with normal Rb1 genes and that the surplus cells were functional, capable of relaying electrical signals to the brain.

Chen said he cultured hair cells that lacked the Rb1 gene and found that they did divide, growing new hair cells, and that the process stopped when the Rb1 protein was added.

Although the studies were only in mice, Chen said the ear structure of the mouse is very similar to that of humans.

The researchers now are screening chemicals that would neutralize the Rb1 protein and, thus, cause hair cells to grow.

“What we want to achieve is just a temporary block of the gene,” said Chen. “When the right number of cells arise, then we would remove the chemical” and halt the hair cell regeneration.

“At the moment, we don’t know how to do that,” said the scientist, and years of more research are needed.

Heller said the Rb1 gene is one of a group of genes that helps control cell growth and without it there is a risk of developing tumors. As a result, he said Chen and his team will have to find a way to switch the gene off only in the cells of the inner ear and then to switch it on again.

“You need to switch it off and on in the right cell,” he said. “Otherwise, you are in trouble.”

On the Net:

Science: www.sciencemag.org




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