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UNLOCKING THE POTENTIAL OF THE EAR

[From House Calls Magazine, House Ear Institute, Los Angeles, CA, Spring, 2007]

Researchers at House Ear Institute have found a clue in their search for potential therapeutic targets to regenerate sensory hair cells in the inner ear to restore hearing. Scientists Patricia White, Ph.D., Angelika Doetzlhofer, Ph.D., Neil Segil, Ph.D., and Andy Groves, Ph.D., discovered that a gene called p27Kip1 is partially responsible for blocking the process of sensory cell regeneration in the mouse hearing organ (cochlea).

Their study identified and tracked p27Kip1 through a new research approach that for the first time purified and characterized in isolation the supporting cells that might have the capacity to divide and generate new hair cells in the deafened ear. Segil and Groves are senior authors of a paper outlining the methods and outcomes of this study published in the June 22, 200 issue of "Nature."

While sensory cells in the hearing organ (cochlea) of birds and other lower vertebrates have the ability to regenerate after being deafened, the sensory cells in the cochlea of humans and other mammals cannot. Researchers in the hearing health field have long investigated possible methods for stimulating hair cell regeneration in humans as a cure for many forms of deafness. Currently, there is no cure for sensorineural hearing loss, which occurs as a result of damage to the cochlea's sensory hair cells from injury, agin, certain medications or infection.

"It's been suspected for a long time that supporting cells will be the key to hair cell regeneration in humans, but this is the first study to really test the ability of supporting cells to divide and turn into hair cells," said Andy Groves, Ph.D. "These study results don't lead directly to the cure for deafness, but they reveal the challenges we'll have to overcome if hair cell regeneration is ever to become a reality."

The investigators developed new techniques to identify and purify supporting cells from mice to test whether they have the capacity to divide, and for how long this capacity persists as mice get older. They found that in newborn mice, p27 was switched off when the cells were grown in a culture dish, and this allowed the supporting cells to divide and make hair cells. In older mice (two weeks old), p27 was not switched off and thus, cell division was blocked. However, when cells were taken from two-week old mice lacking p27, they were once more able to divide and make hair cells. These experiments identified p27 as a block to regeneration and therefore, a possible target for therapy.

"In addition to showing that mammalian auditory supporting cells can turn into hair cells, we've also identified one of the key obstacles that prevent supporting cells in the damaged inner ear from dividing," said Neil Segil, Ph.D. "Our study results suggest that p27Kip1 is one culprit preventing cell division, and thus raises the potential for therapeutically switching it off so that it can't block this necessary part of the regeneration process in the inner ear."