Gene therapy allows a boy, 11, to hear for the first time
Aissam Dam, an 11-year-old boy, grew up in a world of profound silence. He was born deaf and had never heard anything. While living in a poor community in Morocco, he expressed himself with a sign language he invented and had no schooling.
Last year, after moving to Spain, his family took him to a hearing specialist, who made a surprising suggestion: Aissam might be eligible for a clinical trial using gene therapy.
On Oct. 4, Aissam was treated at the Children’s Hospital of Philadelphia, becoming the first person to get gene therapy in the United States for congenital deafness. The goal was to provide him with hearing, but the researchers had no idea if the treatment would work or, if it did, how much he would hear.
The treatment was a success, introducing a child who had known nothing of sound to a new world.
“There’s no sound I don’t like,” Aissam said, with the help of interpreters during an interview last week. “They’re all good.”
While hundreds of millions of people in the world live with hearing loss that is defined as disabling, Aissam is among those whose deafness is congenital. His is an extremely rare form, caused by a mutation in a single gene, otoferlin. Otoferlin deafness affects about 200,000 people worldwide.
The goal of the gene therapy is to replace the mutated otoferlin gene in patients’ ears with a functional gene.
Although it will take years for doctors to sign up many more patients — and younger ones — to further test the therapy, researchers said that success for patients like Aissam could
PHILADELPHIA >> lead to gene therapies that target other forms of congenital deafness.
It is a “groundbreaking” study, said Dr. Dylan K. Chan, a pediatric otolaryngologist at the University of California, San Francisco, and director of its Children’s Communication Center; he was not involved in the trial.
The one in which Aissam participated is supported by Eli Lilly and a small biotechnology firm it owns, Akouos. Investigators hope to eventually expand the study to six centers across the United States.
Aissam’s trial is one of five that are either underway (the others are in China and Europe) or about to start.
Investigators from all five of the studies will be presenting their data on Feb. 3 at a meeting of the Association for Research in Otolaryngology.
The studies, researchers said, mark a new frontier for gene therapy which, until now, had steered clear of hearing loss.
“There has never been a biological or medical or surgical way to correct the underlying biological changes that cause the inner ear to not function,” Chan said.
Although otoferlin mutations are not the most common cause of congenital deafness, there is a reason so many researchers started with it.
That form of congenital deafness, said Dr. John A. Germiller, an otolaryngologist who is leading the CHOP study, is “low hanging fruit.”
The mutated otoferlin gene destroys a protein in the inner ear’s hair cells necessary to transmit sound to the brain. With many of the other mutations that cause deafness, hair cells die during infancy or even at the fetal stage. But with otoferlin deafness, hair cells can survive for years, allowing time for the defective gene to be replaced with gene therapy.
There’s an advantage in using gene therapy to allow children to hear. Most of the mutations that affect hearing — there are approximately 150 — do not affect any other part of the body.
The inner ear is a small closed compartment, so gene therapy delivered there would not affect cells in other parts of the body, said Manny Simons, CEO and co-founder of Akouos and senior vice president of gene therapy at Lilly.
But getting the genes to the cochlea, a spiral-shaped cavity close to the center of the skull, is challenging. The cochlea is filled with fluid, is lined with 3,500 hair cells and is encased in a dense dome of bone with a tiny, round membrane. Sound sets off a wave of fluid in the cochlea and stimulates the hair cells to transmit signals to the brain. Each hair responds to a different frequency.
The gene therapy consists of a harmless virus carrying new otoferlin genes in two drops of liquid that are delicately injected down the length of the cochlea, delivering the genes to each hair cell.
Yet despite the promise of otoferlin gene therapy, finding the right patients for the trial was difficult.