On this page:
- What is gene therapy?
- Is gene therapy for hearing loss available?
- How does congenital hearing loss occur?
- Could gene therapy be used for hearing loss?
- Who could benefit from gene therapy for hearing loss?
- What research does NIDCD support on gene therapy for hearing loss?
- Where can I find additional information about hearing loss?
What is gene therapy?
Gene therapy is a promising treatment that uses genetic material to treat or prevent a disease or medical condition. Gene therapy works by replacing or correcting a defective or missing gene with a healthy version of that gene in cells. In this way, the healthy version of the gene could restore normal cell function.
Is gene therapy for hearing loss available?
While there are currently several active clinical trials that are testing gene therapy for specific forms of hearing loss, gene therapy for hearing loss is not approved by the Food and Drug Administration (FDA) and is not currently available as a potential treatment option for any form of hearing loss in children or adults in the United States.
Up to 60% of congenital (a condition present at birth) and early-onset hearing loss is caused by genetic factors. In the future, gene therapy could potentially restore hearing by targeting genes known to cause hearing loss or deafness.
How does congenital hearing loss occur?
Development of the human auditory system, the sensory system responsible for hearing, begins at about seven weeks of pregnancy. The structures of the auditory system are fully developed at birth, and the brain’s ability to learn to process sound continues after birth in response to sound stimulation. Critical parts of our auditory system are formed during fetal development. These include the cochlea, a tiny snail-shaped structure in the inner ear that receives sound. The cochlea contains hair cells, which are sensory cells that convert sound to electrical signals. These signals are then transmitted by the auditory nerve to the brain, where we recognize and understand sound.
The auditory system must develop and function properly to enable normal hearing. Many genes are responsible for the formation of the auditory system. Any disruptions in structure or function can lead to hearing loss or deafness.
Some genetic variations cause changes in the structure of the inner ear or in the formation of the auditory nerve. Other genetic variations may cause changes in the structure of the hair cells. Sometimes, hair cells may have developed normally, but a genetic variation alters the way they work, preventing sound information from being transmitted to the brain. In each of these cases, hearing loss or deafness can occur.
Could gene therapy be used for hearing loss?
The delivery of gene therapy into the inner ear has the potential to restore hearing in people who have hearing loss caused by genetic variations affecting the development of functional hearing. For gene therapy to work, however, doctors would need to know the exact genetic variation causing the hearing loss, and the therapy would need to be carried out before irreversible changes occur. For some causes of genetic deafness, these changes may occur before birth; in these cases, prenatal therapy may one day be possible and effective.
Other forms of congenital hearing loss can occur when the structure of the inner ear cells develops normally, but a genetic variation in one or more cell types prevents them from working properly. For instance, the hair cells may lack specific proteins that convert sound into electrical signals to send to the brain. In these cases, gene therapy could potentially be administered in the future to children or adults. Depending on the recipients’ age at the time of treatment, and whether they could hear previously, people who receive this therapy might have the challenge of learning to process sound information.
Who could benefit from gene therapy for hearing loss?
Gene therapy for treating hearing loss is not FDA-approved and therefore is not available in the United States. Continued research and clinical trials must first show that such therapies are both safe and effective.
If approved in the future following successful clinical trials, gene therapy could potentially benefit people who are diagnosed with hearing loss caused by a genetic variant. Even then, treatments would likely focus on a type of congenital hearing loss called monogenic. Monogenic hearing loss stems from variations in a single gene and can be inherited. In contrast, polygenic deafness involves multiple genes and potentially environmental factors, making it more complex to treat with gene therapy.
Gene therapy clinical trials are underway for congenital hearing loss caused by variations in a specific gene known as the otoferlin gene (OTOF). Otoferlin is a protein in hair cells that helps convert sound into a signal that can be interpreted by the brain. Otoferlin gene variations cause 1 to 8% of congenital hearing loss cases. When otoferlin does not function correctly, severe to profound hearing loss occurs, despite other functioning hearing structures. Replacing the faulty otoferlin gene with a functioning version could be an approach to restoring hearing in those with otoferlin-related hearing loss.
What research does NIDCD support on gene therapy for hearing loss?
To develop future targets for gene therapy, scientists are investigating the structure, function, and processes of the genes and proteins in the inner ear. NIDCD-supported research has led to the identification of many genes, including otoferlin, that can cause hearing loss when mutated or missing. To date, more than 150 such genes have been identified. As with earlier work on otoferlin, NIDCD-funded researchers are using models to confirm that these genes are potential targets for gene therapy. These studies are essential to defining workable treatments. These are the first steps before eventual clinical trials with human participants.
NIDCD is also supporting natural history studies in people whose hearing loss began in early childhood or in adulthood. One study is investigating the progression of hearing loss in these individuals, with the aim of evaluating whether gene therapy has the potential to address the genetic variation underlying their condition.
Researchers are also working to advance gene therapy technology by developing new methods and delivery systems. Gene-editing technologies, such as CRISPR, could one day be used to modify genes associated with hearing loss. Researchers also aim to unravel the complexities of polygenic (caused by two or more genes) deafness, paving the way for more comprehensive therapies.
If approved for treatment, gene therapy may become one of several options to address genetic hearing loss.
Where can I find additional information about hearing loss?
NIDCD maintains an online directory of organizations providing information on the normal and disordered processes of hearing, balance, taste, smell, voice, speech, and language.
For more information, contact us:
NIDCD Information Clearinghouse
1 Communication Avenue
Bethesda, MD 20892-3456
Toll-free voice: (800) 241-1044
Toll-free TTY: (800) 241-1055
Email: nidcdinfo@nidcd.nih.gov
NIH Pub. No. 24-DC-8226
October 2024