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Jan 17, 2013
 |  BC Innovations  |  Targets & Mechanisms

gamma-Secretase lost and sound

Researchers in Boston and Japan have devised a pharmacological method to transform inner ear epithelial cells into working hair cells and have used the method to restore hearing in deaf mice.1 The finding provides proof of concept for treating hearing loss by manipulating developmental pathways in the adult ear, but figuring out the precise pathway to hit in humans will require further work.

Hair cells in the inner ear transmit sound waves into electromechanical signals sensed by the nervous system. The cells can be damaged by chronic exposure to loud noise and die off in aging adults, leading to age-related hearing loss that affects up to 50 million Americans.

The inner ears of adults with the condition are thought to be functional aside from the dead hair cells. Regenerating those cells has been a goal for the hearing field. Most strategies have focused on restoring hair cells through transplantation or reactivation of latent stem cells.

Now, a Boston-Japan team has proposed an alternative strategy-transdifferentiation of existing epithelial tissue.

In mice, the researchers blocked the activity of notch 1 (Notch1), a developmental factor that influences the differentiation of embryonic stem cells into specialized structures of the cochlea.

"Notch signaling works in the embryo to influence hair cell development," said team leader Albert Edge, associate professor of otology and laryngology at Harvard Medical School and investigator at the Massachusetts Eye and Ear Infirmary. "Embryologists had previously found that development of the cochlear structure uses Notch signaling to turn a layer of undifferentiated epithelial cells into the organ of Corti, which consists of alternating layers of hair cells and supporting...

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