Scientists regenerate the ear’s hair cells to treat hearing loss in mice

Posted by Kerrie Denner

by Carolyn Y. Johnson / Globe Staff

A year ago, I wrote about promising work toward developing a drug that could help treat hearing loss. A group of researchers at Massachusetts Eye and Ear Infirmary had discovered that an experimental drug originally developed with the intent of treating Alzheimer’s disease could regenerate the delicate hair cells inside ears and restore rudimentary hearing when administered to deaf mice.

Albert Edge, an associate professor at Harvard Medical School and Mass Eye and Ear who led the original work, founded Audion Therapeutics, a Dutch startup company to help bring the work to patients while he continued more basic research in his lab. Audion announced this month a deal with the pharmaceutical giant Eli Lilly and Co. that gives the startup the rights to develop certain compounds that Lilly has in its portfolio for use in treating hearing loss. Edge says it may be possible to have the first, small clinical trial testing the safety of a drug within a few years.

Meanwhile, he and his group have continued to try and untangle the basic science behind the process of regenerating hair cells, delicate cells are located deep in the inner ear and sense sound. For years, it had been known that the hair-like sensory cells were regenerated in birds and fish, but not in mammals. The report last year showed that the cells could be triggered to regenerate in mice, and on Thursday in the journal Stem Cell Reports, the team reports new insights into precisely which cells are becoming the new hair cells.

Using cellular markers, the researchers were able to trace the cells that turn into new hair cells. They even found that in newborn mice, some small amount of natural hair cell regeneration occurs after hearing loss caused by damaging antibiotics, which came as a surprise.

“We were doing these experiments in newborns because we knew the newborns were more likely to be responsive to the drug than adults,” Edge said. “We knew that the newborn ears were different than adults, but nobody had shown that spontaneously after damage” regeneration occurred in mammals.

A subset of ear cells that were making a protein called LGR5 were the ones that turned into hair cells, Edge said. That insight won’t likely be useful in the work Audion is doing to try and develop a first-generation drug that could be tested in people, because that drug will not be specifically targeted to one kind of a cell. But the detailed knowledge of how regeneration occurs could help guide future efforts to create drugs and therapies.

“This is really basic work that I think would help more in other future treatments or therapies that we’re working on,” Edge said. His lab is agnostic to what approach to take, trying a range of techniques including gene therapy, cell therapy, and drug therapy. That means that understanding the biological mechanism is important for selecting the therapeutic intervention most likely to work.

Edge said the hope at Audion is that within a few years, a compound could be ready for its first initial safety testing in a small population of patients. Over the years, I’ve gotten a steady stream of e-mails from readers robbed of their hearing desperate for a treatment; when a drug is ready to be tested in people, the company should have no shortage of volunteers.

Source: The Boston Globe


Accessed 2/21/2014

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