Restored. Gene therapy prompts inner-ear hair cells to regrow, restoring hearing to deaf guinea pigs.

Can You Hear Me Now?

For the first time, scientists have managed to restore hearing in a living mammal by using gene therapy to regenerate the delicate hair cells of the inner ear. If the work is replicated, it may be a first step toward a treatment for certain kinds of deafness.

When the sensitive hair cells in the mammalian inner ear are killed, either by loud noise, autoimmune attack, toxic drugs, or aging, the damage is permanent--They don't grow back. Birds and reptiles are luckier: Their damaged hair cells apparently regenerate and can restore normal hearing. Scientists have been searching for ways to replicate this feat in mammals, and recent work has shown that, in culture dishes at least, rat hair cells can be prompted to regenerate when exposed to certain genes.

Building on this work, Yehoash Raphael of the University of Michigan and his colleagues developed a virus containing a developmental gene, called Atoh1, that induces the differentiation of hair cells. To test whether the gene could inspire the regeneration of hair cells in adult animals, the team gave guinea pigs near-toxic levels of a drug that kills hair cells, leaving the animals profoundly deaf. They then injected the virus into the left inner ear of the animals. In a paper published online yesterday by Nature Medicine, the team reports that 2 months after inoculation, the guinea pigs' right ears were still deaf, but the left ears showed signs that some hearing had been restored. When the researchers examined the inner ears of the animals, they saw regenerated hair cells.

The animals' restored hearing is far from normal, Raphael says. The outer ear hair cells, which help the ear to filter different sounds, did not grow back. "What they hear is probably pretty distorted," he says.

Nevertheless, "these appear to be extraordinary results," says Jeffrey Corwin of the University of Virginia in Charlottesville. He cautions, though, that it is notoriously difficult to observe the cells of the inner ear. There is a chance that the drug treatment harmed the hair cells without killing them, he says. But "if the study is correct, and it can be extended, it will be very important."

Related sites
Yehoash Raphael's web site
More on hair cell regeneration from the Society of Neuroscience
Abstract of Nature Medicine paper