The hairs in your ears that help you hear (Image: Gwenaelle S. Geleoc & Artur A. Indzhykulian)

Jumping mice! Seeing them leap in surprise after a blast of loud noise was how a team of researchers could tell that they had cured these mice of their deafness.

“You can’t really ask them if they can hear, so we must use this behavioural trick to find out if they can or not,” says Jeffrey Holt of Harvard Medical School in Boston, Massachusetts – joint head of the team that successfully treated the mice.


Holt’s team is the first to use gene therapy to treat hereditary deafness. Inherited conditions account for at least half of all childhood deafness. More than 70 genes are known to cause various forms of hereditary deafness, but Holt chose to focus on one called TMC1, which accounts for 4 to 8 per cent of cases.

TMC1 forms channels on tiny projections called microvilli in the inner ear, and these channels open when sound waves set the projections in motion. The opening of these channels transmits electrical signals from the inner ear to the brain, and mutations that prevent this from working make a person deaf.

Made you jump!

To tackle the problem, Holt and his colleagues equipped a harmless virus called adeno-associated virus 1 with corrected copies of the faulty gene. Then, they injected a millilitre of solution containing millions of copies of the virus into the inner ears of mice with TMC1 mutations.

Tests on inner ear cells from treated mice showed that the inserted genes were doing their job, permitting the flow of electrical signals when the microvilli were artificially wobbled. Also, using electrodes, the team detected signals in brain regions associated with processing sound signals in treated mice – signals that were absent in untreated mice.

But the “startle test” was the best evidence that the therapy had worked: the mice were suddenly exposed to a loud noise that made treated animals jump a couple of centimetres.

“These new research findings are encouraging and open the door for gene therapies, providing hope for people with certain types of genetic hearing loss,” says Ralph Holme, of the UK research charity Action on Hearing Loss.

The team tested the treatment on two groups of mice –one had TMC1 knocked out altogether, mimicking a common mutation that causes deafness in infants, and the other a different mutation of the same gene that causes deafness by adolescence. They found it worked best in the case that causes deafness in infants, but also showed promise of working in the other condition.

Ears and eyes

Holt is now trying to make the procedure more efficient. The virus successfully loaded the genes into around 90 per cent of inner hair cells, but only 10 per cent of outer hair cells, which are important for dampening or amplifying sounds that are particularly loud or soft. The team also wants to find out whether the effects of the treatment wear off over time, requiring a top-up. “We know they were maintained in the mice for a few months, but we want it to be retained for a lifetime,” says Holt. “If all goes well, we may see clinical trials in the range of 5 to 10 years.”

It might even be possible to use gene therapies to treat hereditary deafness and blindness at the same time, says Holt, because some mutations cause both through a condition called Usher syndrome. Some genes involved in deafness are part of the mechanosensory processes feeding signals to the brain, and so can also affect light receptors in the retina, he says.

“The treatment of hearing loss has been limited to technologies that amplify sound, hearing aids or cochlear implants, but while these provide benefit, the underlying cause of the disorder remains untreated,” says Douglas Brough, the chief scientist of Genvec, a company in Gaithersburg, Maryland, which is currently carrying out human trials of a pioneering gene therapy for acquired hearing loss.

While many people with hereditary deafness are born with their condition, acquired hearing loss gets worse throughout a person’s life, through regular exposure to loud noise or some types of antibiotics that can damage the ears. Genvec’s treatment uses a gene that encourages new hair cells – the type of cell that has microvilli – to grow, and could be suitable for around 1 to 2 per cent of people with this kind of hearing loss. “In my opinion, gene therapy approaches will be a large part of new treatments in the future,” says Brough.

Journal reference: Science Translational Medicine, DOI: 10.1126/scitranslmed.aab1996

When this article was first published, it pointed the finger at the wrong gene for causing Usher syndrome. This has now been changed.