RARE Daily

CHOP Reports Success with First in U.S. Gene Therapy Procedure to Treat Genetic Hearing Loss

January 24, 2024

Rare Daily Staff

Children’s Hospital of Philadelphia said initial results of an experimental gene therapy treatment of an 11-year-old boy with hereditary hearing loss indicate that the treatment was successful, representing a breakthrough in the treatment of patients with hearing loss caused by dozens of different genetic mutations.

“Gene therapy for hearing loss is something that we physicians and scientists in the world of hearing loss have been working toward for over 20 years, and it is finally here,” said John Germiller, an attending surgeon and director of clinical research in the Division of Otolaryngology at CHOP, and associate professor at Perelman School of Medicine at the University of Pennsylvania. “While the gene therapy we performed in our patient was to correct an abnormality in one, very rare gene, these studies may open the door for future use for some of the over 150 other genes that cause childhood hearing loss.”

CHOP is one of several clinical trial sites in the world participating in the AK-OTOF-101 clinical trial, sponsored by Akouos, a subsidiary of Eli Lilly and Company.

The boy in the study was born with otoferlin gene (OTOF)-mediated hearing loss and was the first patient to receive this gene therapy in the study. In October, he underwent a surgical procedure at CHOP where the gene therapy was placed into the inner ear using a device called an endoscope that allows the ear drum to be partially lifted to enable insertion of the therapy into a tiny entry point in the cochlea. A single, small dose of a gene therapy (AK-OTOF) containing copies of the normal OTOF gene was then delivered directly to the inner ear. This delivery method represents the first time a gene therapy has been used as a potential treatment for hereditary hearing loss in the United States.

The patient was born deaf in both ears. Now, almost four months since receiving the investigational gene therapy in one ear, the patient’s hearing has improved enough that he now has only mild to moderate hearing loss in the ear that was treated. The patient is able to hear sound for the first time in his life. He can hear his father’s voice, the sound of a car passing by and even the scissors clipping his hair.

There are more than 150 different genes that have been implicated in hearing loss, and about 1 in 500 newborns are affected by some form of genetic hearing loss.

The gene therapy for children with OTOF-mediated hearing loss has been designed to restore hearing by delivering copies of normal OTOF genes into the inner ear. With normal OTOF genes, the sensory cells will be able to function so they can respond to sound and activate the auditory nerve to send impulses to the brain. Functioning OTOF genes are encased in a viral vector, a modified form of a non-disease-causing virus, which allows them to be delivered into cells of the cochlea in the inner ear.  The vector solution is directly injected into the internal fluid of the cochlea during the procedure.

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