Hearing loss - easy to prevent but hard to cure

She has spent decades doing basic research on hearing and what actually happens when hearing damage occurs. And it seems to work something like this: It is estimated that there are over 16,000 hair cells in the inner ear. Hair cells are activated when they are hit by sound waves, and then they release transmitter substances that are picked up by nerve fibres, the outermost projections of the ear's neurons. Each hair cell communicates with about 20 nerve fibres that together transfer the signals through the neurons to the auditory cortex of the brain.  

But hair cells are progressively reduced by natural ageing. They then no longer function properly.  

And that is not all. Many nerve fibres also retract. When shortened, they are no longer as accessible to the decreasing amount of neurotransmitters. 

This increasing distance between crucial cells in the cochlea is primarily affected by age and noise. But it can also occur as an effect of certain medicines and chemicals, or for other reasons such as infections or blows to the head.  

“We have seen in studies on mice that when they are exposed to moderate noise for about two hours, these nerve fibres retract. But they can come back to a certain extent,” says Barbara Canlon.  

And when they come back, they are again accessible to neurotransmitters. By then, the sense of hearing has partially recovered from the noise damage. 

But if the noise exposure happens again and again and again - repeatedly - then the nerve fibres are unable to recover. They will be permanently shortened. And at the same time, the hair cells may be reduced in number.  

Then the hearing loss will be permanent, at least without treatment. Intensive research is underway to find new ways to save hearing. 

How researchers are trying to save hearing

One challenge is that the pea-sized cochlea hides its secrets behind a tough shell. It is also located several centimetres inside our hard skull bone - making it more difficult to examine it than the brain itself.  

“The cochlea is so inaccessible that studies on human cochlea are rare. This is why virtually all hearing research is done on animals, especially mice. This means that we know less about how human hearing works than we know about human vision, for example,” says Barbara Canlon.  

The ongoing global research is still at a fairly basic level, a bit away from having treatments ready. But attempts are being made - and common research goals are to medically enable nerve fibres to pass on signals despite no longer receiving input from hair cells. Or, as Barbara Canlon and her colleagues have done, awaken the hair cells using gene therapy. 

They are not the first to use their specific approach; ten years ago it was already used by American researchers who induced hearing in mice with congenital deafness. The mice had a genetic abnormality that prevented them from producing the protein VGLUT3, one of the substances involved in communication between hair cells and nerve fibres. It became global news that the researchers had injected a virus containing the gene for the protein directly into the cochlea, resulting in deaf mice being able to hear. But it is unclear how long the effect lasted. It seems that it was not lifelong. 

“This suggests that if this were to develop into a treatment, it would probably need to be repeated at certain intervals. But giving an injection into the cochlea requires a small operation. I find it hard to see people wanting to go through that on a regular basis,” says Barbara Canlon.  

She and her colleagues have found another way to get the protein into the cochlea. By injecting it into the back of the head, at a point where it is possible to come into contact with the fluid flowing around and in the brain, the cerebrospinal fluid. That fluid also flows into the so-called cochlear aqueduct, which leads into the cochlea. And researchers have shown that the treatment actually reaches the cochlea through an injection in the back of the head, which is less invasive than an injection directly into the cochlea.  

In the previous experiments with injections directly into the cochlea, the mice were newborn, partly because the bones surrounding the cochlea are softer at birth, facilitating the injection. But the Swedish researchers used adult mice. And they also started to hear.  

“Promising,” says Barbara Canlon.  

“The next step is to conduct experiments on primates. We have contacted a research group that has a group of monkeys of various ages. We want to see if we can get effects on age-related hearing loss. It is possible to imagine that hearing may not be restored, but that the hearing can be partially saved so that a hearing aid will have a better effect,” says Barbara Canlon. 

The younger the children are, the better the results.  

“The age of surgery is the most important factor when it comes to deaf babies. But there are lots of other important factors, such as how much you use the implants and how much you are talked to, which differs between families and preschools. But we also think that it may matter what the nerve bundle looks like, how thick it is,” says Eva Karltorp. 

She and her team are now studying, among other things, the language abilities of teenagers born deaf who received CIs as children. One study has already shown that children born deaf who had surgery before the age of nine months have similar language development to children born hearing, measured at the age of four.  

Follow-up is now done on children who have had early surgery and have reached adolescence. Researchers look at perceived quality of life, grades in school and how well it is going with friends. They also conduct demanding spoken language tests that examine, for example, the understanding of non-literal phrases and figurative language. The results have not yet been published.  

Previous studies have shown that at the group level, children with CI have more difficulty repeating so-called non-words, nonsense words without meaning. For example, if someone says “hepe blird” or “blarf cule”, children with CI generally have more difficulty repeating the words. The importance of being able to repeat non-words is not fully understood, but it is still considered to be linked to language impairment.  

“These children's hearing works differently than the hearing in children born able to hear. And we know that there are individual differences. One question to pursue is whether this is something that can be influenced. Can operations be carried out even earlier? Or could the nerves need some additional stimulation? We do not know that today,” says Eva Karltorp.   

About 4,500 people in Sweden live with cochlear implants. About 1,000 of them are children. Eva Karltorp has operated on about a thousand patients, both children and adults.  

“I met one of those I operated on as a baby the other day. He was now studying at university and followed all the lectures. You would never have noticed that this person had a hearing loss, there was nothing in the conversation to indicate that.”