Gene therapy restores hearing to 11-year-old boy

Gene therapy restores hearing to 11-year-old boy


Born deaf, he expressed himself with a sign language he invented. But for Aissam, life changed thanks to a clinical trial: he had nothing to lose, having grown up in a world of profound silence. But gene therapy worked for him. He is 11 years old and he can feel, as if he has been doing it forever.

What sparks hope about the effectiveness of new treatments for congenital deafness is the clinical case of a child born deaf told by New York Times, the first to receive gene therapy in the United States. The goal was to make him feel it, but the researchers had no idea whether the treatment would work and, if so, how much.

Aissam’s story

Aissam was born in a poor community in Morocco, he never went to school and last year he moved to Spain, to Barcelona, ​​where he was visited for the first time and included in the experimentation of Eli Lilly, conducted by the biotechnology company Akouos. He was hosted at the pharmaceutical company’s expense for four months with his father in Philadelphia, where last October he received an injection of Ak-Otof gene therapy directly into the cochlea, a spiral-shaped cavity near the center of the skull. And he returned to hearing with one ear, the only one treated as required by the research protocol.

A rare form of deafness

His was an extremely rare form of deafness, caused by a mutation in a single gene, otoferlin, which affects approximately 200,000 people worldwide. But already there are a number of candidates waiting for a call, although for now newborns and adolescents will be excluded, as well as all those who have bilateral cochlear implants, which is the first form of support provided to those born deaf. The device, which uses electrodes to stimulate auditory nerves in the inner ear, alters the cochlea in some way, which could hinder the interpretation of gene therapy results during the trial. But success on Aissam could lead to developing gene therapies aimed at other forms of congenital deafness.

Five experiments

This is just one of five experimental otoferlin mutation trials that are underway or about to begin. The new treatment won’t help all deaf people, only those who have a mutation in the gene that destroys a protein needed to transmit sound vibrations from the ear to the brain. Four children with a similar disorder have already been successfully treated in Shanghai thanks to a gene injected by researchers at Fudan University via a harmless viral vector, which restored their hearing in both ears.

A similar trial by Regeneron Pharmaceuticals has already been given the green light and will involve children in the US, UK and Spain. And Eli Lilly also intends to expand the research, in the United States and Taiwan, just as in France they are working to start a new one, after the success of the testing on mice.

The functioning of the ear

“There is no biological, medical or surgical way to correct the non-functioning of the inner ear. The only strategies available to us today are the cochlear implant and, in less serious cases or in which it is not feasible, prosthetics. positive is that they work well and give excellent results, especially if they are combined with early screening from birth”, explains Dr. Paolo Tavormina, director of Otolaryngology at the Regina Margherita children’s hospital in Turin. “Today we have the possibility of ascertaining congenital deafness in a few months and of intervening within the first year of life, in order to allow normal psycho-intellectual development. A child who does not hear will become a child who does not speak, which is why today the test is performed bilateral cochlear implantation as soon as possible, so as not to impact brain development.”

Congenital deafness

While otoferlin mutations aren’t the most common cause of congenital deafness, there’s a reason many researchers started here. This mutation only affects hearing, and not other body functions, so this gene therapy is the one that, theoretically, shows the least unexpected side effects, since it would not affect cells in other parts of the body. Another advantage is that in otoferlin deafness the hair cells survive for years, giving the defective gene time to be replaced with gene therapy, while in other forms the auditory tissues are already inactive at the fetal stage.

The first noises

“No one knew whether the nerve cells that communicate with the hair cells of Aissam’s cochlea were still intact,” explains Dr. Manny Simons of Akouos, head of Eli Lilly’s gene therapy trial. “It wasn’t even clear to us what dose of genes we should administer.” But even though it was a “blind” attempt, Aissam’s father confirmed that the child started hearing traffic noises just a few days after the treatment. And when he underwent an audiology test two months after the infusion, his hearing in the treated ear was nearly normal. The noises initially scared him, he said. But then he began to enjoy every sound he heard: elevators, voices, the clicking of scissors cutting his hair, and music, which he heard for the first time while he was at the hairdresser.

The language

This enormous success may, however, preclude Aissam from being able to speak. After the age of 5, learning language is almost impossible for the brain, but there are already two younger children waiting to receive the same treatment, both three years old, one from Miami and one from San Francisco, who have the cochlear implant in one ear, which makes the other ear treatable. “Hypocusis is a truly vast area, and any therapy capable of correcting a gene alteration is certainly important and can improve the lives of many people – concludes Tavormina -. But only if it can be offered in a safe and early way it will be possible to make a difference, without impacting in any way on the development of language.”



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