Hope for Hearing Loss?

By Rachel Zelkowitz

Sensitive ears. Mice that received extra copies of a protein during fetal development produced more of a key hearing cell (bottom) than control mice did.

Credit: David Woessner, John Mitchell, and John V. Brigande

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A cure for hearing loss could be closer, now that a team of scientists has produced key ear cells in mice--and for the first time verified that the cells work just like natural ones.

The inner ear turns sound waves into electrical signals inside the organ of Corti, which is lined with rows of 15,000 to 20,000 hairlike cells. The cells respond to vibrations by producing electrical impulses that travel via nerves to the brain. It's a fragile system; loud noises can damage the hair cells and age can deplete them, resulting in hearing loss. Researchers guessed that they could restore some hearing by replacing those hair cells. Previous studies isolated a protein called Atoh1, which triggers hair-cell growth. But it wasn't clear that the engineered cells would have the same mechanical and electrical properties as normal ones when produced in an animal.

To address that concern, John Brigande, a developmental neurobiologist at Oregon Health and Science University in Portland, and colleagues injected embryonic mice with DNA containing several copies of Atoh1. The researchers inserted the genes about a week before birth--after they could identify tissue that would become the inner ear and before the natural development of hair cells had begun. Four days after the mice were born, the researchers examined their hair cells.

Mice that produced the extra Atoh1 had almost twice as many hair cells as did control mice, the researchers report today in Nature. Electron microscopy revealed that the extra hair cells were divided into inner and outer hair cells, just like the normal ones, and they made the same proteins. Next, the researchers determined that the engineered cells responded to sound waves and turned them into electrical signals.

The findings show that Atoh1 replacement therapy can produce viable hair cells in animals, Brigande says. "That's exciting because it offers a strong rationale to pursue cell-replacement strategies for hearing loss."

Other auditory experts agree. Matthew Kelley, a developmental neuroscientist at the National Institute on Deafness and Other Communication Disorders in Bethesda, Maryland, applauds the method of introducing the Atoh1 during the embryonic stage. "It's a brand-new technique. This has been one of the major challenges and roadblocks in inner ear research."

Yehoash Raphael, an auditory neuroscientist at the University of Michigan, Ann Arbor, says the findings provide a new delivery model for researchers trying to use developmental genes to restore lost hearing. But before researchers can develop a treatment for humans, they have to answer questions such as how many copies of Atoh1 are necessary to stimulate hair-cell regrowth and what is the best way to deliver the gene to a human organ of Corti.