An 11-year-old boy who was born deaf in both ears due to a genetic mutation that affects 200,000 people worldwide has undergone genetic therapy for congenital deafness in the United States that has made him able to hear. The little boy participated in a clinical trial testing this experimental therapy, so the researchers did not know a priori whether the treatment would be successful, or how much hearing it would provide the patient.
The patient is Aissam Dam, a boy born in Morocco who has communicated throughout his life through an invented sign language, according to the American media The New York Times. Last year he moved to Spain with his family and was taken to a hearing specialist, who deemed him a candidate to participate in a clinical trial testing gene therapy.
On October 4, Aissam was treated at Children’s Hospital of Philadelphia (CHOP) and became the first person to receive gene therapy for congenital deafness in the United States. The treatment was a success and allowed a child who knew nothing about sound to discover a new universe: “There is no sound that I don’t like,” “they are all fine,” Aissam declared with the help of interpreters during an interview last week. pass.
“Gene therapy for hearing loss is something that doctors and scientists in the hearing loss world have been working on for more than 20 years, and it is finally here,” said surgeon Dr. John A. Germiller. assistant and director of Clinical Research in the Division of Otolaryngology at CHOP and Associate Professor at the Perelman School of Medicine at the University of Pennsylvania. “While the gene therapy we performed on our patient was to correct an abnormality in a very rare gene, these studies may open the door for future use in some of the more than 150 genes that cause childhood hearing loss.”
Congenital deafness caused by the mutation of the otorpheline gene
Aissam deafness is an extremely rare form caused by a mutation in a single gene, otoferlin (OTOF). Otoferlin deafness affects about 200,000 people worldwide. The goal of gene therapy is to replace the mutated otoferlin gene in patients’ ears with a functional gene.
On October 4, 2023, the patient underwent a surgical procedure at CHOP where gene therapy was placed in the inner ear using a device called an endoscope that allows the eardrum to be partially lifted to temporarily insert an investigational medical device: the “round window”, a small entry point to the cochlea. A small, single dose of a gene therapy (AK-OTOF) containing copies of the normal OTOF gene was then administered directly to the inner ear. This delivery method represents the first time a gene therapy has been used as a potential treatment for inherited hearing loss in the United States.
Now, almost four months since receiving the experimental gene therapy in one ear, his hearing has improved enough that he has only mild to moderate hearing loss in the treated ear and has been able to hear a sound for the first time in his life. . Although hearing loss can be caused by different factors, such as disease, injury, aging, exposure to loud noises, or malformations of the inner ear, it can also be caused by a variety of genetic mutations. So far, more than 150 different genes are known to be responsible for hearing loss, and approximately one in every 500 newborns is affected by some type of genetic hearing loss.
“These studies may open the door for future use in some of the more than 150 genes that cause childhood hearing loss.”
Gene therapy for children with OTOF-mediated hearing loss is designed to restore hearing by introducing copies of normal OTOF genes into the inner ear. With normal OTOF genes, sensory cells will be able to function to respond to sound and activate the auditory nerve to send impulses to the brain. The functional OTOF genes are encased in a viral vector, a modified form of a non-disease-causing virus, which allows them to enter the cells of the cochlea in the inner ear. The vector solution is injected directly into the internal fluid of the cochlea during the procedure.
CHOP is one of several clinical trial sites around the world participating in the AK-OTOF-101 clinical trial, sponsored by Akouos, Inc., a wholly owned subsidiary of Eli Lilly and Company. This research trial is being conducted in collaboration with CHOP’s In Vivo Clinical Gene Therapy group, a multidisciplinary team of experts committed to advancing transformative human therapies and building on CHOP’s legacy as a leader in innovative gene therapy.
Dr. Germiller developed a cutting-edge, minimally invasive, endoscopic round window surgical approach at CHOP 10 years ago for infants and toddlers undergoing a different diagnostic procedure in the round window of the cochlea. The delivery approach used for this gene therapy procedure, developed by Akouos and enabled by an investigational delivery device being developed in parallel with the gene therapy, leverages this prior work.
“As more patients of different ages are treated with this gene therapy, researchers will learn more about the degree to which hearing improves and whether that level of hearing can be maintained for many years,” Germiller said. “What we have learned from following this patient’s progress will help direct our efforts to help as many patients as we can,” she concludes.
