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Scientists Show Mouse Ear Holds Potential for Cell Regeneration to Restore Hearing

Article on possible new targets for future gene therapy to restore hearing published in NATURE

Los Angeles - June 21, 2006 - 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 Neil Segil, Ph.D., and Andy Groves, Ph.D., discovered that a gene called p27Kip1blocks the process of sensory cell regeneration in the mouse inner ear (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, 2006 issue of Nature magazine.

While sensory cells in the inner ear (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, aging, 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., researcher at House Ear Institute. "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."

"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., researcher at House Ear Institute and associate professor of research at the University of Southern California Medical School. "Our study results suggest that p27Kip1 is one culprit preventing cell division, and this 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."

The investigators used newly developed 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, 2 weeks old mice, p27 was not switched off and thus, cell division was blocked. However, when cells were taken from 2 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.

The lead co-authors of the paper are Patricia M. White, Ph.D., Angelika Doetzlhofer, Ph.D, postdoctoral fellows in the Gonda Department of Cell and Molecular Biology at the House Ear Institute (HEI). The study was funded by a five-year grant from the National Organization for Hearing Research (NOHR).

About the House Ear Institute

The House Ear Institute (HEI) is a private, non-profit 501(c)(3) organization dedicated to advancing hearing science through research and education to improve quality of life. Established in 1946 by Howard P. House, M.D., as the Los Angeles Foundation of Otology, and later renamed for its founder, the House Ear Institute has been engaged in the scientific exploration of the auditory system from the ear canal to the cortex of the brain for 60 years. Institute scientists continue to explore the developing ear and ear diseases at the cell and molecular level, as well as the complex ear-brain interaction. They are also working to improve hearing aids, diagnostics, auditory implants, clinical treatments and intervention methods. For information on the House Ear Institute, please call (213) 483-4431 or visit the Website at www.hei.org .

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