Andrea Warner-Czyz, Ph.D., CCC-A
You might have heard about gene therapy as a treatment option for children who are deaf or hard of hearing and wondered if your child might be a candidate. First, let’s review how the ear works and what can make it not work. Then, let’s cover how gene therapy works for a specific type of hearing loss. Finally, we will summarize what parents should know about gene therapy as a possible treatment for their child’s hearing loss.
In an ear with typical function, sound waves enter the outer ear and get turned into mechanical vibrations in the middle ear. The smallest bone in your body, the stapes, passes on information from the mechanical vibrations in the middle ear as it pushes into the snail-shaped cochlea of the inner ear. In the cochlea, fluid flows over the cochlear hair cells, which “bend” to create electrical signals that stimulate the spiral ganglion cells of the auditory, or hearing nerve. Many factors can affect how the auditory system functions and can result in hearing loss, but not all causes of hearing loss have the potential to be treated with gene therapy.
The gene that has received the most attention relative to gene therapy for hearing loss is called OTOF. The OTOF gene provides the code for a protein called otoferlin, which mediates if and how the information from the inner ear gets to the auditory nerve. Children with two non-functioning OTOF genes often have severe-to-profound sensorineural hearing loss at birth or hearing loss that progresses to severe-to-profound levels in the first few years of life. When the OTOF genes do not function properly, the cochlear hair cells continue to work like a typically hearing ear, but the signal does not travel normally to the auditory nerve and, consequently, the brain. This can result in a pattern of test results characteristic of a condition called auditory neuropathy, which affects a small group of children (<8% of all cases of congenital deafness).
A few research teams worldwide have developed otoferlin-based gene therapy, which presents a healthy copy of the human OTOF gene to the cochlea to replace the non-functioning copies of the OTOF gene and restore the transfer of information from the inner ear to the auditory nerve. Although these gene therapies differ relative to surgical approach, all house the healthy copy of the OTOF gene in what is called an adeno-associated viral vector, and all yield similar results across more than 50 individuals who have received OTOF-based gene therapy. Recently published peer-reviewed literature reports that approximately 80-90% of pediatric participants have recovered some hearing, with most showing improved thresholds in behavioral pure-tone or auditory brainstem response testing from profound levels to mild-moderate levels. Some children have achieved near-normal hearing levels, speech recognition, and sound localization within a few months of treatment. Most improvements in hearing occur within the first six months after treatment, although incremental changes may occur through 2.5 years post-treatment. Earlier this year, the Food and Drug Administration approved the use of lunsotogene parvec (Otarmeni), an OTOF-related gene therapy for congenital hearing loss related to auditory neuropathy. Otarmeni is the first, and presently only, approved gene therapy for hearing loss.
This summer, a clinical trial targeting a second cause of genetic hearing loss, the GJB2 (gap junction beta-2) gene, was initiated. The GJB2 gene makes Connexin 26, a protein that forms cell-to-cell channels, allowing ions and electrolytes to transfer from one cell to another. A defect in the GJB2 gene results in the most common genetic cause of severe-to-profound sensorineural hearing loss at birth. Similar to the OTOF-related treatment, the GJB2-related treatment consists of a surgical procedure, placing the gene therapy product into the cochlea of the participant. The first child received the GJB2-related gene therapy injection in August 2026.
What should parents know
- Current clinical trials and the newly FDA-approved use of Otarmeni for gene therapy applies to a small number of individuals who are deaf or hard of hearing with OTOF-related hearing loss of severe-to-profound and profound levels, which is associated with auditory neuropathy.
- OTOF-related gene therapy reflects a safe treatment with few adverse events.
- Vast variability exists in outcomes, from partial to full recovery of hearing, and we need more research to clarify which factors relate to better recovery.
- If an individual has the diagnosis of congenital hearing loss because of the OTOF genetic defect they should consider contacting an authorized treatment center for Otarmeni or a center participating in the clinical trial for OTOF-related gene therapy (https://www.otarmenihcp.com/gtx/find-an-authorized-treatment-center).
- A new clinical trial with GJB2-related hearing loss of severe-to-profound degree is under way. The effectiveness of this treatment is undetermined at the present time.
- If an individual has the diagnosis of congenital hearing loss because of the GJB2 genetic defect, they should consider contacting a center participating in the clinical trial for this condition.
The question arises as to whether parents should delay cochlear implantation for their child to wait for future inner ear therapeutics. Current gene therapies have limited scope (i.e., OTOF) and high variability in recovery of auditory function. Moreover, several questions still exist related to gene therapy as a treatment for pediatric hearing loss: Will a single dose suffice, or will children need future boosters? Which factors serve as risk or protective factors for the hearing obtained? Will gene therapy recipients have increased vulnerability to damage their hearing from excessive noise, ototoxic agents, or aging? Can individuals who undergo gene therapy use hearing technologies such as hearing aids and cochlear implants?
While future research will help answer questions such as these, the answers will not come quickly. It will take years before the safety and effectiveness of these gene-based therapies for hearing loss is apparent, and FDA approval is obtained. In the interim, families are encouraged to promptly discuss treatment options with an ENT or neurotologist who specializes in pediatric hearing loss. Early access to sound is important for auditory and spoken language development, and families should work with their care team to determine the best option for their child.