Harvard Medicine

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Back from the Dead

Sound progress is being made in efforts to regenerate sensory cells.

Hearing aids and cochlear implants bring sound into the lives of many with hearing loss. Both devices compensate for missing hair cells and auditory neurons, the delicate structures of the inner ear that receive, amplify, and translate sound into electrical signals to be processed by the brain. But these devices treat the symptoms of the loss, not the cause.

RIDE THE WAVE: Bundles of sensory cilia, such as these from the inner ear hair cells of a guinea pig, sway in response to sound vibrations, stimulating nerve impulses that travel to the brain, where they are interpreted as sound.<br/><br/>Photo by Dr. David Furness/Wellcome Images

Researchers at the Massachusetts Eye and Ear Infirmary (MEEI) and the Harvard Stem Cell Institute hope to offer patients another treatment option—drug cocktails that coax the inner ear into growing new sensory cells. Albert Edge, an HMS associate professor of otology and laryngology at MEEI, and his colleagues study adult stem cells of the cochlea. Although these cells initially divide and transform into sensory cells, by puberty they become inactive.

Edge’s team maps the process by which these stem cells develop specific functions, identifying factors that push them toward particular fates. The Edge lab and other groups have discovered, for example, that activation of the transcription factor Atoh1 transforms cochlear stem cells into hair cells. Working at the Harvard NeuroDiscovery Center, Edge’s team applied more than 100,000 chemicals one by one to cell colonies and identified roughly a hundred that boost Atoh1 levels. Next, they must validate the findings in cochlear stem cells.

“Our ultimate goal is to identify chemicals that will activate patients’ endogenous stem cells,” says Edge. “We may need to administer a series of compounds to the inner ear to achieve this result.”

That effort would also require sophisticated vehicles for delivering drugs to the cochlea, which hides behind a blood-perilymph barrier. Led by Michael McKenna of MEEI and Jeffrey Borenstein of MIT and Draper Laboratory, a team of auditory scientists and engineers—including Sharon Kujawa and William Sewell, both HMS associate professors at MEEI—has created one possible candidate. Working in guinea pigs, the researchers are developing a remote-controlled device that sits behind the ear in the mastoid cavity and stores drugs in a reservoir. At the press of a button, the device releases the drugs, which travel through a tube that winds from the middle ear into the cochlea.

“We can use this device to infuse the inner ear with drugs that prevent the degeneration of sensory cells,” says McKenna, an HMS professor of otology and laryngology. “After we learn more about the endogenous stem cells, we can tackle those too.”


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