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Newborn during hearing screening
Photo: ASTIER / BSIP / IMAGO
It was a very special moment in Assaim Dam's life. After gene therapy at Children's Hospital in Philadelphia, Pennsylvania, the 11-year-old was recently able to hear for the first time in his life. "There's no sound I don't like," Assaim told the New York Times, "they're all good."
Assaim's successful treatment is also something special for Tobias Moser. Moser is professor of auditory neuroscience at the Georg-August University in Göttingen. And the fact that there is now an option for healing for children like Assaim who were born deaf is largely due to a discovery by Moser and his colleagues.
Assaim, who was born in Morocco, inherited a defective copy of a gene from his parents that provides the blueprint for a certain protein. As a result, his body cannot produce this protein called “otoferlin”. However, the protein plays an important role in the transmission of sound information from the sensory cells in the inner ear to the auditory nerve - researcher Moser discovered this around twenty years ago. Anyone affected by this type of Otoferlin hearing loss hears poorly or not at all.
A so-called cochlear implant (CI) can bridge the severed connection. Children who are given such hearing aids early enough often learn to speak just as well as their hearing peers. However, such therapy was not available for Assaim in his home country and he will probably no longer learn to speak. There is only a limited window of time during infancy for normal language development. According to the New York Times, Assaim answered journalists' questions using sign language.
But much younger children have also been cured of their Otoferlin hearing loss with the help of gene therapy, as has now been revealed. Chinese researchers reported on this in the journal “The Lancet” on January 24th. In their study, three girls and three boys aged between two and a half and five years received the treatment. Five of the children improved their hearing threshold and speech comprehension.
For researcher Moser, the rapid development is "a crazy feeling," he says. "It doesn't often happen in a researcher's life that a fundamental discovery actually leads to therapy." In the treatment of hearing loss, says Moser, "that is likely a real turning point.«
Based on his findings, Moser's former Göttingen colleague Ellen Reisinger, who is now researching at the University Hospital of Tübingen, had found a way to introduce the blueprint for the missing protein into the inner ear of mice with Otoferlin hearing loss - using special viruses as a means of transport.
Moser and his colleagues continue to research this treatment on marmosets, as they are evolutionarily closer to humans than rodents. Among other things, he wants to know: Is the repair of the hearing system via gene therapy permanent or does the effect wear off again?
Moser is still concerned that pharmaceutical companies are already treating people with gene therapy, especially children. "It happened faster than I ever thought possible," says Moser, "there's a lot of drive behind it now." Children will also soon be treated in Great Britain and France. Among the companies that have brought the researchers' approach into clinical use are biotech start-ups; little Assaim was treated with a therapy from the start-up Akouos, which has since been taken over by the pharmaceutical giant Eli Lily.
Companies will soon be competing for suitable candidates: Otoferlin hearing loss is comparatively rare. Severe hearing loss and deafness are the most common congenital sensory impairments. They affect one in 1000 newborns. In order to be able to treat them early, for example with hearing aids or CIs, babies' hearing is tested shortly after birth in a so-called hearing screening in many countries.
But there are more than 140 genetic changes that can affect hearing. Otoferlin hearing loss is just one of them. “The special thing about this form of genetically determined hearing loss is that the hair cells in the inner ear are preserved,” explains scientist Moser, “which opens up the possibility of treating the cause of the hearing loss.” In many other hereditary forms of hearing loss, important structures already go during embryonic development. If hearing loss is diagnosed after birth, the window of opportunity for causal treatment has already closed.
Moser has now also set up a patient register together with the human geneticist Barbara Vona from Götingen. For a certain form of Otoferlin hearing loss, adults could also benefit from gene therapy. Although these patients can hear, the lack of the protein apparently causes them to have impaired sound processing. Speech, for example, sounds distorted to her, "as if you were making a phone call over an extremely disturbed cell phone connection," explains the ear, nose and throat doctor. Gene therapy could possibly benefit such patients.
Moser believes it is unlikely that the method will be able to completely overcome deafness in the near future. “Cochlear implants work well, we will need them for the foreseeable future,” says the researcher. He is therefore also working on improved variants of neuroprostheses. With such optogenetic CIs, sound is not transmitted via electrical impulses, but rather with the help of light. This approach also uses gene therapy in the inner ear to make the auditory nerve sensitive to light. In this way, frequencies could be resolved more highly: This would make it easier to understand speech in noisy environments and also to perceive music.