The ability to hear is an important ability for a species living in society, such as humans. This is a key function for understanding and interacting with fellow human beings. However, hearing depends on a fragile system that quickly breaks down when exposed to increasingly noisy environments. Almost 1.5 billion people around the world suffer from hearing loss, and in France there are 6 million people who are hard of hearing.
This disease affects all segments of the population, although the elderly are mostly affected (65% of people aged 65 years and older suffer from hearing loss compared to 6% of people aged 15-24). To combat this scourge, two methods are used today, depending on the severity of its severity: hearing aids and hearing implants. For mild hearing impairment, a simple hearing aid that serves as a sound amplifier is sufficient. But when it’s too loud, this simple external tool only allows the user to hear distorted sounds. This is because his lack of hearing is rooted deep in his cochlea, an organ deep inside his ear that translates sounds into auditory signals, which are then transmitted to the brain via the auditory nerve.
For the treatment of these cases of profound deafness, ear implants are preferred because they transmit sounds through electrical signals inside the cochlea using electrodes. These methods have proven effective, but have never allowed their users to regain normal hearing: they are a palliative, but by no means a solution to the problem of deafness.
As part of Sound Week, which takes place in January 2023, a conference was organized at UNESCO on January 18, dedicated to four innovative treatments aimed at definitively curing hearing loss.
1) Gene therapy, the preferred solution for overcoming deafness
The most advanced work in finding cures for deafness has focused on the building blocks of life. Researchers have been working for decades to identify genes whose mutations can lead to sensorineural deafness, which affects the inner ear. To date, researchers have identified 134 genes responsible for as many forms of sensorineural hearing loss.
The ability to hear is an important ability for a species living in society, such as humans. This is a key function for understanding and interacting with fellow human beings. However, hearing depends on a fragile system that quickly breaks down when exposed to increasingly noisy environments. Almost 1.5 billion people around the world suffer from hearing loss, and in France there are 6 million people who are hard of hearing.
This disease affects all segments of the population, although the elderly are mostly affected (65% of people aged 65 years and older suffer from hearing loss compared to 6% of people aged 15-24). To combat this scourge, two methods are used today, depending on the severity of its severity: hearing aids and hearing implants. For mild hearing impairment, a simple hearing aid that serves as a sound amplifier is sufficient. But when it’s too loud, this simple external tool only allows the user to hear distorted sounds. This is because his lack of hearing is rooted deep in his cochlea, an organ deep inside his ear that translates sounds into auditory signals, which are then transmitted to the brain via the auditory nerve.
For the treatment of these cases of profound deafness, ear implants are preferred because they transmit sounds through electrical signals inside the cochlea using electrodes. These methods have proven effective, but have never allowed their users to regain normal hearing: they are a palliative, but by no means a solution to the problem of deafness.
As part of Sound Week, which takes place in January 2023, a conference was organized at UNESCO on January 18, dedicated to four innovative treatments aimed at definitively curing hearing loss.
1) Gene therapy, the preferred solution for overcoming deafness
The most advanced work in finding cures for deafness has focused on the building blocks of life. Researchers have been working for decades to identify genes whose mutations can lead to sensorineural deafness, which affects the inner ear. To date, researchers have identified 134 genes responsible for as many forms of sensorineural hearing loss. Thus, by conducting molecular diagnostics, scientists should be able to implant this gene through a viral vector into cells that represent mutations that underlie hearing loss. “We have already managed to perform this operation on mice with the gene encoding otoferlin. This is significant progress,” said Christine Petit, a human genetics biologist and professor at the Pasteur Institute, during the conference. Otoferlin is a protein that plays an important role in the transmission of sound information at the level of synapses of the hair cells of the inner ear. However, this work, although promising, could only be done on rodents with immature snails. In humans, the maneuver is more difficult because the snail is already mature at birth and no such work has been done on this type of snail so far.
Diagram of the inner ear. Credits: Bruno Bourgeois/Sciences et Avenir
2) Optogenetics: with the help of light you can hear
Other directions were presented at the conference by Ann-Lise Giraud, a neuroscientist specializing in language and speech.
Optogenetics, which involves using light signals to activate genetically modified cells to be light-sensitive, was at the heart of two projects supported by the Pasteur Institute. The use of this technique can, in particular, replace the electrodes used for conventional implants. The team of Professor Jérémy Barral, a researcher at the CNRS and the Institute of Hearing, is working on the creation of luminous cochlear implants that provide information transmission accuracy that is not possible with electronic stimulation.
However, to create this innovative alternative, scientists still have to overcome a number of challenges. To make this implant functional, the researchers must design a grid of microscopic light sources inserted directly into the cochlea. Until this breakthrough is achieved, it is unlikely that illuminated cochlear implants will appear in the ears of the hearing impaired for some time to come.
Devices that pay attention to hearing don’t stop at the inner ear. Another project led by Bryce Batelier, a researcher at the CNRS and the Hearing Institute, is the development of an implant that is placed directly into the auditory cortex. This technology aims to encode light patterns in the brain to create sounds. The team at this project, called Hearlight, has already done this sort of experiment on mice and succeeded in encoding artificial sounds in their auditory cortex, whose neurons had previously been made light-sensitive, by exposing it to different photonic patterns representing different sounds. To make this technology compatible with the human brain, flexible and biocompatible instruments will need to be developed, since the auditory cortex is located within the temporal gyrus and is therefore difficult to access. To meet this challenge, Brice Batelier’s team still has many years of research and development ahead of them.
3) Sens-401: drug for the treatment of sudden hearing loss.
Instead, other researchers are working on a biomolecular solution to treat deafness. Sensorion has launched a research program to produce a drug that can treat sudden neurosensory disturbances. This product is based on the Sens-401 molecule. So far, this has only been tested in laboratory rats. After severe hearing loss and approximately thirty days of treatment, the guinea pigs recovered 30 to 20 decibels versus less than 10 in the placebo-treated rodents. During the conference, Naval Uzren, General Manager of Sensorion, confirmed that this product is in the process of obtaining approval for clinical trials this year.
4) Using stem cells to replace damaged cells.
While treatments at the molecular level seem promising, another type of treatment focuses on cells. Christine Petit presented cell therapy methods for the treatment of deafness during the conference. “We found that there are progenitor cells in the cochlea whose fate can be changed,” emphasizes Christine Petit. These stem cells play a supportive role in the cochlea, but they can be transformed into sensory cells that can potentially replace defective ones. However, such an operation poses a risk of uncontrolled proliferation, and so far injections of cells into the inner ear have only been performed in rodents.
Much of the work to cure deafness is still in its infancy, but many possibilities are already open. “All actors in the hearing research sector must come together so that new therapies find fertile ground,” insists Christine Petit.