Gene Therapy Restores Hearing for Deaf Baby

(Posted on Tuesday, June 4, 2024)

The tale of Opal Sandy, a deaf baby, has captured widespread interest. Restoring her hearing through gene therapy holds potential for individuals with genetic deafness and other inherited conditions. This offers a beacon of hope where conventional treatments have fallen short. 

Opal Sandy was born with a genetic impairment for hearing; in normal circumstances, she could expect to be deaf her whole life. Gene therapy has changed that dramatically as it has enabled her to hear.

Understanding the Anatomy and Genetics of Hearing

Understanding hearing loss involves the intricate processes within the ear, particularly in the cochlea. Here, specialized hair cells are crucial in converting sound vibrations into electrical signals transmitted to the brain. However, genetic mutations can disrupt this intricate process, leading to deafness. In fact, most hearing loss in children can be traced back to these genetic mutations.

Caption: Diagram of the Anatomy of the Ear

In cases of profound hearing loss caused by otoferlin gene mutations like Opal experienced, the problem originates in the cochlea’s inner hair cells. Inner hair cells convert sound vibrations into electrical signals, and otoferlin facilitates the release of neurotransmitters from these cells to the auditory nerve fibers, transmitting auditory signals to the brain. The gene contains instructions for creating the otoferlin protein, essential for communicating between inner ear cells and auditory nerve fibers. 

When mutations occur in both gene copies, the inner hair cells cannot produce functional otoferlin protein. This disrupts the release of neurotransmitters from the hair cells, preventing the proper transmission of sound signals to the auditory nerve fibers. As a result, we experience hearing loss.

Otoferlin gene therapy aims to solve this problem by directly introducing a working gene to the cochlea’s inner hair cells. The goal is to help the body produce more otoferlin protein, essential for restoring communication between the inner ear cells and the auditory nerve fibers.

The CHORD Trial: An In-Depth Look

Opal participated in the CHORD trial, a global phase 1/2 clinical study. The study aimed to evaluate gene therapy for children with severe hearing loss caused by otoferlin gene mutations. The main goal was to determine if gene therapy could help restore hearing in both ears by targeting the defective otoferlin gene using an adeno-associated virus vector. We will describe this in much more detail in a related story.

Caption: Diagram of how the treatment is done in the CHORD trial by Regeneron and Decibel Therapeutics.

The trial involved administering a low dose of gene therapy in one ear and gradually increasing the dose in later phases. The treatment involved a single injection into the inner ear, or cochlea, under general anesthesia, similar to the procedure for cochlear implantation. The vectors are designed to work in the cochlea’s inner hair cells. After being injected into the cochlear fluid, the inner hair cells are targeted and take up the vectors. These vectors then release the DNA containing the correct otoferlin gene, which enables the production of the otoferlin protein. The production of this protein leads to the restoration of hearing.

Study Methods and Limitations

The methodology of the CHORD trial is rigorous and carefully structured to ensure safety and efficacy. At first, the treatment was given to one ear to see what happened and to reduce any possible adverse effects. The initial results were promising, with Opal showing significant improvement in her hearing abilities within weeks of the treatment. Within 24 weeks after the treatment, Opal’s hearing in the treated ear improved from profound deafness to nearly normal levels for her age. Opal can now hear soft sounds like a whisper, and her hearing is “close to normal,” with an average improvement of 80 decibels from baseline.

However, like all pioneering medical interventions, this study has its limitations. The trial is still in its early phases, and long-term data on the durability of the treatment and its potential side effects are not yet available. Additionally, as with any gene therapy, there is a risk of immune reactions and other unforeseen complications.

Implications for the Future

The success of this gene therapy provides a promising glimpse into the future of treating genetic hearing loss. For individuals with otoferlin gene mutations, this therapy could be an alternative to cochlear implants, which, while effective, do not fully replicate natural hearing. Gene therapy aims to restore normal physiological hearing by addressing the root cause of the hearing loss.

While the future of gene therapy looks promising, it is essential to approach it realistically. Challenges such as high treatment costs, ethical considerations, and potential long-term effects must be addressed. Extensive research and clinical trials are necessary to ensure the safety and efficacy of these therapies. The medical community must also navigate regulatory hurdles and secure funding to bring these treatments from the lab to the clinic.

A Positive Outlook for the Future

In essence, Opal Sandy’s story is a powerful reminder of the potential of science. It also serves as a call to action for medical professionals, researchers, and policymakers to support and advance gene therapy, ensuring that more individuals benefit from these treatments.

—–

This story is part of a series on the current progression in Regenerative Medicine. In 1999, I defined regenerative medicine as the collection of interventions that restore tissues and organs damaged by disease, injured by trauma, or worn by time to normal function. I include a full spectrum of chemical, gene, and protein-based medicines, cell-based therapies, and biomechanical interventions that achieve that goal.

In this subseries, we focus specifically on gene therapies. We explore the current treatments and examine the advances poised to transform healthcare. Each article in this collection delves into a different aspect of gene therapy’s role within the larger narrative of Regenerative Medicine. 

To learn more about regenerative medicine, read more stories at www.williamhaseltine.com