Hearing repaired: gene therapy restores guinea pigs' hearing.

By flipping on a gene that's normally active only during embryonic development, researchers have restored hearing to a group of profoundly deaf guinea pigs. The finding may lead to treatments for millions of people with acquired hearing loss, the team says.

Like people, guinea pigs use auditory hair cells, found deep inside the inner ear, to detect sounds. When sound waves reach them, the cells' hairlike projections sway with the vibrations and transmit electrical signals to the brain's auditory center.

Permanent damage to the sensitive cells by aging, diseases, certain medications, and even loud sounds is the most common cause of acquired hearing loss in people. "The only biological way to induce recovery is by generating new hair cells," says Yehoash Raphael of the University of Michigan Medical School in Ann Arbor.

Two years ago, Raphael and his colleagues succeeded in regrowing hair cells in adult guinea pigs (SN: 6/7/03, p. 355). However, the team had no evidence that the new hair cells detected sound or connected properly with the brain.

To see whether healing is restored, the researchers expanded on their previous experiment. They started by giving a group of normal-hearing guinea pigs large doses of drugs known to degrade hearing in people and other animals. Three days later, microscopic photos of the animals' inner ears confirmed that the drugs had destroyed all the auditory hair cells, leaving the animals profoundly deaf.

Raphael's team then inserted a virus carrying the mouse version of a gene called Atoh1 into the left inner ears of some of the animals. Atoh1, formerly known as Math1, is normally expressed during embryonic development in cells destined to become hair cells. Once hair cell growth is complete in an embryo, the gene shuts off permanently.

After 8 weeks, the researchers reexamined the guinea pigs for signs of new hair cells and hearing. Animals that weren't treated with the engineered virus showed no change. However, the left ears of treated animals had new hair cells. When Raphael's team measured those animals' auditory brain stem response, a test also used on people, the researchers found that hearing had returned in the treated animals. Raphael and his colleagues will publish their findings in an upcoming Nature Medicine.

"This is a truly remarkable study that ... everyone will be talking about for awhile," says Zheng-Yi Chen of Harvard Medical School in Boston. Chen's team reports in an upcoming Science another experiment that could lead to a treatment for heating loss. By eliminating the gene that normally stops embryonic development of hair cells in mice, the researchers caused the cells to continue being produced even after birth.

Chen says that a combination of approaches such as his and Raphael's may eventually treat different types of heating loss in people.

In the meantime, Raphael and his colleagues are tweaking their technique to perfect the guinea pigs' newfound hearing, which they describe as "distorted." They also plan to test whether gene therapy can restore heating to guinea pigs deafened by age or noise exposure and whether their method is effective when there's a significant delay between heating loss and treatment.