THERE is a glimmer of hope for the millions of people who lose their hearing every year because of damage to the sound-detecting hair cells in the inner ear. Gene therapy has been used to generate new hair cells in guinea pigs.
鈥淭hat is quite a big breakthrough,鈥� says hearing expert Alec Salt of Washington University in St Louis. He thinks the procedure should be easy to repeat in humans, with minor modifications, since the inner ears of guinea pig are very similar to those of humans.
But although neurons grew towards the new hair cells, it is not yet clear if the guinea pigs could actually hear with them. It will also be important to find out whether the new cells are oriented in the right way. Some hearing problems are caused by misorientation of hair cells, rather than damage, says Matthew Kelley of the National Institute on Deafness and Other Communication Disorders in Rockville, Maryland, whose team recently discovered a gene necessary for the correct orientation of hair cells.
Advertisement
Auditory hair cells act like microphones, converting sounds into nerve signals that are then relayed to the brain. They can be damaged or destroyed by loud noises, infections or ageing. And in mammals, once they have been lost they do not grow back. Cochlear implants can bypass the damaged hair cells and directly stimulate the nerves. But they are only suitable for some people with severe hearing loss and require a three-hour operation, with all the risks that entails. And even the best cochlear implants do not come close to restoring normal hearing.
Several groups have been racing to figure out how to regenerate hair cells. Yehoash Raphael at the University of Michigan in Ann Arbor and his colleagues in the US and Japan are the first to succeed. They used an adenovirus to add temporarily a copy of a gene called Math1 to the cells lining the fluid cavity in the inner ear of 14 guinea pigs. The gene would have been active for a few days before being broken down. Math1 was chosen because it is involved in helping young ear cells decide to become auditory hair cells. Cells in which Math1 is switched on turn into hair cells, while cells in which it remains switched off become non-sensory cells.
What surprised the team was that the gene can teach old non-sensory cells new tricks. About a month after the virus was injected into guinea pigs, new hair cells could even be seen in places near the organ of Corti in the inner ear where there are usually none. It appears that when Math1 was switched on, non-sensory cells actually changed their identity (The Journal of Neuroscience, vol 23, p 4395).
There is still much to do before the method can be tried in people. But Raphael believes the ear is a promising organ for gene therapy. It is isolated from the rest of the body, for example, so gene-carrying viruses can be injected where they are needed and should not end up elsewhere. Also, Math1 does not stimulate cell division, so it is unlikely to trigger cancer directly. However, there is concern that even viruses that rarely integrate into the genome might disrupt active genes, which could cause cancer (鈥淔resh blow for gene treatments as safety of a second virus is questioned鈥�).
Even if the technique proves successful at restoring hearing, not everyone will welcome it. Some deaf people refuse cochlear implants for themselves or their children, regarding them as a threat to deaf culture.