People who have lost their hearing will be injected with a harmless virus carrying a gene that should trigger the regrowth of their ears’ sensory receptors

Fully functional (Image: Steve Gschmeissner/SPL)

IN TWO months’ time, a group of profoundly deaf people could be able to hear again, thanks to the world’s first gene therapy trial for deafness.

The volunteers, who lost their hearing through damage or disease, will get an injection of a harmless virus containing a gene that should trigger the regrowth of the sensory receptors in the ear.

The idea is that the method will return a more natural sense of hearing than other technologies can provide. Hearing aids merely amplify sounds, while cochlear implants transform sound waves into electrical waves that the brain interprets, but they don’t pick up all of the natural frequencies. This means people can find it difficult to distinguish many of the nuances in voices and music.


“The holy grail is to give people natural hearing back,” says Hinrich Staecker at the University of Kansas Medical Center, who is leading the trial. “That’s what we hope to do – we are essentially repairing the ear rather than artificially imitating what it does.”

The holy grail is to give people natural hearing back – that’s what we hope to do by repairing the ear

There are still many things we don’t know about how the ear works. This is because the delicate machinery of the inner ear is enclosed in the hardest bone in the body, making it difficult to isolate without causing damage.

What we do know is that sound waves are funnelled into the ear, making the ear drum vibrate. These vibrations are transferred to the cochlea in the inner ear via three tiny bones. Thousands of sensory receptors line a part of the cochlea called the organ of Corti, as rows of inner and outer hair cells. Sound waves, amplified by the outer hair cells (shown above right), vibrate the inner hair cells, opening ion channels on their surface that let neurotransmitters flow in. This triggers electrical activity in the cochlear neurons, passing the information to the brain so it can be processed.

Both inner and outer hair cells can be damaged by loud noises, drugs such as some antibiotics and disease, and don’t regrow. A possible fix arose in 2003, when researchers discovered that certain genes can transform the cells supporting the hair cells into both types of hair cell.

To see whether one of these genes, called Atoh1, could be used to improve hearing, last year Staecker and colleagues inserted it into a harmless virus and injected that into the cochlea of mice that had had almost all of their hair cells destroyed. Two months later, the rodents’ hearing had improved by about 20 decibels. “This is about the same difference between hearing with your hands over your ears, and what you hear ordinarily,” says Lloyd Klickstein, head of translational medicine at Novartis, the Swiss drug company collaborating on the trial.

Staecker’s team have now got the go-ahead to do the same in people. In the next month, they will begin searching for about 45 volunteers who have severe hearing loss, most likely caused by the side effects of drugs. This group will have lost a large number of hair cells, but will still have supporting structures, such as neurons, present in the inner ear. “The biggest risk is that we interfere with residual hearing, so we’re starting with people who have lost almost all hearing already,” says Klickstein.

People between the ages of 18 and 70 will be eligible for the trial. Those who are born deaf won’t be because they often don’t have the structures needed to support hair cells. Staecker estimates that the approach could help 1 to 2 per cent of all people with hearing loss, up to 7 million people in the US.

Sticking plasters

The trial will start at the University of Kansas Medical School before being widened to other institutions. As with the mice, the team will inject the viral gene package directly into the volunteers’ cochlea by peeling back their ear drum and passing a needle through a tiny hole made by a laser (see diagram). The Atoh1 gene should reach the supporting cells, instructing them to divide and form new hair cells. Results are expected between two weeks and two months later.

“Today’s medical treatments are largely limited to hearing aids and cochlear implants, which are essentially just sticking plasters,” says Ralph Holme, head of biomedical research at UK charity Action on Hearing Loss. “This is why the planned trial is extremely encouraging and offers hope to the millions affected by hearing loss that a cure is possible.”

Jeffrey Holt at Harvard Medical School, who isn’t involved in the trial, calls it ground-breaking and says he is cautiously optimistic about the work. “Hopes are high that the trial will yield positive results without introducing unnecessary complications.”

The only expected side effect is a brief period of dizziness or nausea, a common occurrence after ear surgery. In pre-clinical tests, Novartis researchers looked to see if the virus spread to any other tissues, but found it was restricted to the site of injection. It has also been designed to have limited potential to recombine with the volunteer’s DNA so it is unlikely to cause problems elsewhere.

Many other species, such as fish and birds, can regenerate the hair cells in their inner ear over time and create new auditory circuits, says Klickstein. “We’re just trying to tweak the mammalian system a little bit to do what a lot of other species do naturally”.

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This article appeared in print under the headline “Let there be sound”