Children’s Hospital of Philadelphia Performs First in U.S. Gene Therapy Procedure to Treat Genetic Hearing Loss

Children’s Hospital of Philadelphia (CHOP) is proud to announce the initial results of an experimental gene therapy treatment of a patient with hereditary hearing loss in the United States. Findings to date indicate that the treatment was successful. While the gene involved is quite rare, the milestone represents a breakthrough in the treatment of patients around the world with hearing loss caused by dozens of different genetic mutations and marks another innovative move for gene and cell therapy in a new area of medicine

“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 A. Germiller, MD, PhD, 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.”

An eleven-year-old born with otoferlin gene (OTOF)-mediated hearing loss was the first patient to receive this gene therapy in the study. On October 4, 2023, the patient 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, allowing an investigational medical device to be transiently inserted into the “round window,” a tiny entry point into 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 profoundly 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 literally hearing 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.

While hearing loss can be caused by a variety of factors, like illness, injury, aging, exposure to loud noises or malformations of the inner ear, it can also be caused by a variety of genetic mutations. To date, more than 150 different genes have been implicated in hearing loss, and about 1 in 500 newborns are affected by some form of genetic hearing loss.

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.

CHOP is one of several clinical trial sites in 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 the Clinical In Vivo Gene Therapy group at CHOP, a multidisciplinary team of experts committed to advancing transformative human therapies and building upon CHOP’s legacy as a leader in breakthrough 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 on the cochlea’s round window. The delivery approach that is 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 earlier work.

“As more patients at different ages are treated with this gene therapy, researchers will learn more about the degree to which hearing is improved and whether that level of hearing can be sustained over many years,” Germiller said. “What we have learned from following this patient’s progress will help direct our efforts toward helping as many patients as we can.”

To learn more about this clinical trial, visit the study.