2024-02-01 02:00:05
Aissam Dam was born deaf and lived in a poor community in Morocco Hannah Beier/The New York Times Aissam Dam, an 11-year-old boy, grew up in a world of profound silence. He was born deaf. He had never heard a sound. While living in a poor community in Morocco, he had no schooling and expressed himself with a sign language he invented. Last year, after moving to Spain, his family took him to a hearing specialist, who made a surprising suggestion: Aissam met the necessary requirements to participate in a clinical study using gene therapy. On October 4, Aissam was treated at Children’s Hospital of Philadelphia, becoming the first person to receive gene therapy for congenital deafness in the United States. The goal was to give him hearing, but researchers had no idea whether the treatment would work or how much he would hear if the therapy worked. The treatment ended up being a success, introducing a new world to a child who knew nothing about sounds. During an interview last week, Aissam, with the help of interpreters, said: “There’s no sound I don’t like. They’re all good.” Although there are hundreds of millions of people in the world who live with hearing loss defined as disabling, Aissam is among those whose deafness is congenital, that is, when the baby is born deaf, having acquired deafness during pregnancy, due to causes that occur in the prenatal, perinatal or postnatal periods. Its form is extremely rare, caused by a mutation in a single gene, the otoferlin protein. Deafness resulting from otoferlin affects around 200,000 people worldwide. The goal of gene therapy is to replace the mutant otoferlin gene in patients’ ears with a functional gene. Although it will take years for doctors to select more candidates – young people, in particular – to test the therapy on a larger scale, researchers say the success of patients like Aissam could lead to the development of gene therapies that target other forms of congenital deafness. “It’s an innovative study,” said Dr. Dylan K. Chan, a pediatric otolaryngologist at the University of California, San Francisco, and director of the Center for Children’s Communication, who was not involved in the experiment. In October 2023, the 11-year-old boy was treated at Children’s Hospital of Philadelphia Hannah Beier/The New York Times The trial in which Aissam participated is supported by Eli Lilly Pharmaceuticals and a small biotechnology company he owns, Akouos. Researchers hope to expand the study to six medical centers in the United States. Aissam’s experiment is one of five that are ongoing (others are in China and Europe) or about to begin. Researchers from the five studies will present their data on February 3 at a meeting of the Association for Research in Otolaryngology. They said the current studies mark a new frontier for gene therapy that, until now, has only prevented hearing loss. “There has never been a medical, biological or surgical way that can correct the underlying biological changes that cause the inner ear to not function,” noted Dr. Chan. Although otoferlin mutations are not the most common cause of congenital deafness, there is a reason why so many researchers began their investigations into it. “This form of congenital deafness is the fruit of the tree closest to the ground”, commented Dr. John A. Germiller, an otolaryngologist leading the Chop study, at Children’s Hospital of Philadelphia. The mutant otoferlin gene destroys a protein in the hair cells of the inner ear, which are needed to transmit sound to the brain. With many of the other mutations that cause deafness, hair cells die during infancy, or even in the fetal stage. But in otoferlin deafness, hair cells have a chance to survive for years, giving time to replace the defective gene with gene therapy. There is an advantage to using gene therapy to allow children to hear. The majority of mutations that affect hearing – there are approximately 150 – do not affect any other part of the body. Some genes are actually unique to the ear. Because the inner ear is a small closed compartment, gene therapy delivered there does not affect cells in other parts of the body, explained Manny Simons, CEO and co-founder of Akouos and senior vice president of gene therapy at Lilly. Aissam’s experiment is one of five that are ongoing or about to begin Hannah Beier/The New York Times The challenge is to get the genes to the cochlea, a spiral-shaped cavity near the center of the skull. The organ responsible for auditory function, it is filled with liquid, covered by 3,500 hair cells and surrounded by a dense bony dome with a tiny, round membrane. The sound triggers a wave of fluid in the cochlea and stimulates hair cells to transmit signals to the brain. Each wire in it responds to a different frequency, allowing the person to hear the richness of the sound. Gene therapy consists of a harmless virus that carries new otoferlin genes in two drops of liquid that are gently injected along the cochlea, delivering the genes to each hair cell. However, despite the good promise of otoferlin gene therapy, it was difficult to find the right patients for the trial. One obstacle was the very idea of treating deafness. “There is a community among the deaf that does not believe in the need for a cure,” said Dr. Robert C. Nutt, a developmental and behavioral pediatrician in Wilmington, North Carolina, who is deaf. Some deaf parents, he added, celebrate when their newborn’s hearing test indicates that their baby is also deaf and can therefore be part of their community. To make the issue of gene therapy more complicated, there is also the standard intervention for otoferlin hearing loss: a cochlear implant. This consists of a device that uses electrodes to stimulate the auditory nerves in the inner ear. Allows the patient to hear sounds, especially those necessary for understanding speech. But the implant does not provide the full richness of the sound; aids hearing, but does not completely restore it. Most babies born with otoferlin deafness receive a cochlear implant in infancy and this does not allow them to participate in the study. The implant alters the cochlea somewhat, which can make it difficult to interpret the results of gene therapy. The U.S. Food and Drug Administration (FDA) allowed the Chop study to move forward but asked that, for safety reasons, investigators start with older children, not infants, and treat just one ear. . According to his doctors, Aissam’s results were remarkable Hannah Beier/The New York Times The challenge of the study in the United States is to find older children whose parents agree to the treatment, have otoferlin deafness and do not have a cochlear implant. Aissam has never had a cochlear implant. In Morocco, she never studied to the point of developing communication skills. Three years ago, when she was 8, her father, Youssef Dam, a construction worker, got a job in Barcelona, Spain. For the first time, Aissam was able to study, enrolling in a school for the deaf, where she learned Spanish Sign Language. Soon after, her family learned about the gene therapy trial. When Aissam was deemed eligible to be patient number one, the companies Lilly and Akouos paid for him and his father to live in Philadelphia for four months while the boy received gene therapy and follow-up hearing tests. According to his doctors, Aissam’s results were remarkable. In an interview given at the Children’s Hospital of Philadelphia, her father – who speaks a North African language from the Amazigh family, commonly known as Berber – said, through an interpreter, that Aissam was able to hear traffic noises a few days after the treatment. When he had a hearing test two months later, his hearing in the treated ear was close to normal. But no matter how well the gene therapy works, researchers recognize that Aissam may never be able to understand or speak a language, said Dr. John Germiller, explaining that the brain has a narrow window to learn to speak from the age of two to three. After five, the window for learning spoken language is permanently closed. Asked if there was any sound in particular that he liked, Aissam responded by signs, without hesitation: “The sound of people.”
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