New hope for the hard of hearing

The hair cells of the inner ear are vital but fragile, and they can easily be damaged. Up to now, the consequences have largely been irreversible, but gene therapy research on mice embryos shows promise of a cure - although many hurdles remain.

Actors William Shatner, left, and Leonard Nimoy have suffered from hearing problems for more than four decades since an explosion on the Star Trek set damaged their ears.
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There are few things more important - but also more fragile - in a person's body than the hair cells of the ear. Sitting inside the cochlea of the inner ear, these cells help to convert the vibrations of the middle ear into electrical signals sent to the brain. Unfortunately, a string of factors, some of them beyond our control, can damage these delicate cells beyond repair. Loud noise, certain drugs, infection and the effects of age are all harmful to hair cells and, in turn, damaging to hearing. In addition, some individuals have genetic abnormalities that mean the hair cells never function correctly in the first place.

As the hair cells are unable to regenerate themselves, one bout of loud noise or a nasty infection can leave a person hearing impaired for the rest of their life. Just ask actors Leonard Nimoy and William Shatner, who have both suffered for more than four decades with hearing loss and the associated ringing in the ears called tinnitus. Their problems started when a special effects explosion on the set of Star Trek, in which they starred, damaged Nimoy's right ear and Shatner's left.

Up to now such hearing loss caused by damage to the inner ear's hair cells has largely been incurable. But there could be hope on the horizon, thanks to research of the kind recently published in the journal Nature by a team of US scientists. The group at Oregon Health and Science University used gene therapy to grow functioning inner ear cells in mice embryos in the womb. Gene therapy involves inserting a functional form of a gene into cells that are not expressing that gene, often because the individual carries a defective form of the gene.

In the Oregon research, when virus particles were used to transfer a gene called Atoh1 into the inner ear of unborn mice, the animals ended up with more hair cells than normal. And importantly, the cells that had Atoh1 added to them functioned in the same way as normal hair cells. The results come on the back of similar laboratory breakthroughs by other scientists using gene therapy with an array of animals.

Five years ago, for example, scientists at the University of Michigan used gene therapy to generate hair cells in adult guinea pigs. In addition, the new hair cells stimulated the growth of associated nerve cells. In addition, there has been progress in developing stem cell treatments for hearing loss. Last year, researchers found that injecting bone marrow stem cells into the inner ears of rats with damaged hearing speeded recovery.

Dr Mark Downs, director of science at Britain's RNID, formerly the Royal National Institute for the Deaf, believes it is "no longer just a pipe dream" to talk about cell-based treatments to restore hearing in humans. "There is a long way to go, but the journey towards new treatments is certainly under way," he says. However, there are a range of hurdles to be overcome before people with hearing problems start to benefit from gene therapy treatments.

Among them is actually delivering the hair cell genes into the inner ear of the recipient, whether a human embryo or an actual person. In either case, there would be a major surgical procedure. "Doing it in a mouse in utero is one thing, doing it in humans in utero is another matter," says Dr Jonathan Gale, a lecturer in cell biology at the Ear Institute at University College, London, "Some kind of surgery to plant something into the inner ear - I think that would be the way people might think about it, yes.

"There are also ways of delivering via windows in the middle ear that involve much less invasive surgery than trying to inject into the inner ear." Even if the cells could be delivered into the patient's inner ear, and made to grow new hair cells, that person's hearing would not necessarily be restored to normal. "You have to be very careful because the experimental approach [on embryos] is very different from having somebody who might have been gradually going deaf through age-related hearing loss or had suffered hearing loss through noise months or years before," Dr Gale says. If somebody has been deaf for a long period of time, it might be that you have to regenerate many structures in the ear. We don't know enough about that."

There could also be complications in using gene therapy to cure tinnitus, according to Professor Alan Palmer, assistant director of the UK Medical Research Council's Institute of Hearing Research based in Nottingham, England. Some forms of tinnitus are the result of the loss of hearing at particular frequencies due to damage to the inner ear cells from age, noise or other factors. The fact that hearing is affected at certain frequencies more than at others, Professor Palmer explains, causes a reorganisation of the auditory cortex, the part of the brain that processes sound, and complex changes in the neurotransmission of sound signals.

The parts of the auditory cortex that would have detected frequencies for which the person has lost hearing continue to be stimulated, only this time by what is known as an "edge frequency", a phantom signal produced by the absence of genuine sound. If the damage to the cochlea's hair cells could be reversed through gene therapy, Professor Palmer says, the person's hearing might return to normal, causing the tinnitus to disappear.