Breakthrough Hero

There’s a lot to celebrate in Philadelphia — an 11-year-old was able to hear for the first time through gene therapy! Children’s Hospital of Philadelphia (CHOP) was thrilled to share the preliminary outcomes of an experimental gene therapy intervention for a patient in the United States with hereditary hearing loss. As of January 23, 2024, the initial results suggest the treatment has been a success.

While this achievement signifies a major advancement in addressing hearing loss stemming from various genetic mutations globally, we must note that the gene involved is very rare. However, although the implicated gene is uncommon, it’s an exciting day for the use of gene and cell therapy and its use in a new area of medicine.

The Surgeon Says

According to attending Surgeon John A. Germiller, M.D., Ph.D., Director of Clinical Research in the Division of Otolaryngology at CHOP, as well as an Associate Professor at Perelman School of Medicine at the University of Pennsylvania, “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.” It’s amazing to think that we are seeing the realization of gene therapy for hearing loss in our day and age. It is a culmination of more than two decades of efforts by physicians and scientists in the field of hearing loss. Germiller added, “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.”

How They Did It

The first recipient of the gene therapy in this study was an 11-year-old diagnosed with otoferlin gene (OTOF)-mediated hearing loss. On October 4, 2023, the patient went into surgery for the procedure at CHOP. During surgery, using an endoscope, the gene therapy was introduced into the inner ear. The endoscope is what allowed the eardrum to be partially lifted, which allowed a medical device to be put into the “round window,” an entry point into the cochlea that is very tiny.

A tiny dose of a gene therapy (AK-OTOF), which contained copies of the OTOF gene (copies that were “normal”), was then placed directly to the inner ear. This approach marks a groundbreaking use of gene therapy in the United States, as a potential remedy for hereditary hearing loss.

The Immediate Outcome

Born with profound deafness in both ears, the patient underwent investigational gene therapy almost 4 months ago (in just one of his ears). Miraculously, his hearing has significantly improved, and he now experiences only mild to moderate hearing loss in the ear that underwent surgery. This transformative outcome means that, in short, the patient can now hear. For the first time in his life, he can do something as basic as getting a haircut, and it’ a new experience because he can hear the sound of the scissors clipping his hair. Then there are the not-so-basic, wonderous things like hearing his father’s voice. He has heard things most people take for granted and has delighted in them, like the sounds of a car passing by.

Everyone involved in the project has high hopes that this marked progress is only the beginning. “What we have learned from following this patient’s progress will help direct our efforts toward helping as many patients as we can,” added Dr. Germiller, his eyes looking ahead to helping more and more people with this gene therapy.

When considering the source of hearing loss we see in our day-to-day lives, most of us will assume it’s either age-related or noise-related hearing loss, or maybe hearing loss due to illness, injury, inner-ear malformations, or various illnesses. Genetic mutations causing hearing loss don’t come up very much. While the patient’s genetic disorder is rare, there are more than 150 genes that have been proven to cause hearing loss. Looking at newborns, about 1 in 500 are affected by some form of genetic hearing loss.

With his eyes firmly set on the future, Dr. Germiller explained, “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.”
Included as part of the worldwide AK-OTOF-101 clinical trial, CHOP serves as one of several clinical trial sites. Sponsoring the trial is Akouos, Inc., a wholly owned subsidiary of Eli Lilly and Company. Working together with CHOP is another team called Clinical In Vivo Gene Therapy group. It’s a multidisciplinary team dedicated to advancing revolutionary human therapies. The research aims to build upon CHOP’s legacy as a trailblazer in breakthrough gene therapy.

A decade ago at CHOP, Dr. Germiller developed a pioneering, state-of-the-art, and minimally invasive endoscopic round window surgical technique for infants and toddlers. These young patients were undergoing a distinct diagnostic procedure on the cochlea’s round window. The current breakthrough gene therapy our 11-year-old newly-hearing patient just had success with most definitely draws upon the advancements made in this earlier surgical approach.

It’s always a great day when doctors and scientists can see success built upon earlier projects. It’s easy to lose sight of the fact that each seemingly little piece of progress they make along the way is just a building block for all the amazing things they will bring to fruition in the future. Today, gene therapy is helping an 11-year-old hear for the first time; maybe tomorrow we find a cure for age-related hearing loss. Who knows?

If you have hearing loss, make sure to bring it to the attention of an expert audiologist in your area. Any kind of hearing loss brings with it other issues, as it’s linked to other conditions such as cognitive decline and depression. Keeping your hearing health at its peak will ensure you keep your quality of life at the level you desire.