Gene Therapy for Hearing Loss in Children

Gene therapy for hearing loss is an area of clinical research focused on very rare, genetic forms of hearing loss in children. In these conditions, changes in a child’s DNA affect how the inner ear develops or functions, leading to hearing loss that is present at birth or early in life.

Unlike current treatments that help children make better use of available sound — such as hearing aids or cochlear implants — gene therapy is being studied as a way to address and treat the underlying genetic cause of hearing loss. Most approaches are still considered investigational and are offered only through carefully controlled clinical trials. There is currently only one specific form of genetic hearing loss with an available therapy, but there may be more available in the future.

Because gene therapy only targets very rare genetic causes of hearing loss, it is not the right solution for every child. Families begin by scheduling a clinical evaluation with a pediatric otolaryngologist to learn whether gene therapy could be an option.

Gene therapy is a technique used to treat or prevent a condition by targeting its genetic cause. Genes contain instructions that tell cells how to make proteins, which carry out many of the body’s essential functions.

When a gene has a variant (also called a mutation), the instructions it provides may not work as intended. Gene variants can lead to proteins that are missing, faulty, or produced in the wrong amount. This can interfere with normal cell function and contribute to disease. Gene therapy aims to address this problem by changing how genes function in the body, such as by adding a working copy of a gene, modifying how a gene is expressed, or correcting a disease-causing genetic change.

Gene therapy is being studied for genetic forms of hearing loss, including some types of congenital hearing loss that are present at birth and inherited forms that run in families. In these forms of hearing loss, gene mutations lead to changes in protein expression and interfere with how the inner ear develops or functions.

Initial research has focused on mutations in the OTOF gene, which represent only a very small percentage of children with hearing loss. The OTOF gene provides instructions for making otoferlin, a protein involved in sound signal transmission within the inner ear. When this process does not work as expected, hearing loss may be present at birth or begin early in life. These approaches are still considered investigational and are offered through carefully designed clinical trials. They are not appropriate for most people with hearing loss.

Gene therapy is not designed to treat hearing loss caused by non-genetic factors, such as infections, head trauma, or exposure to loud noise. Current approaches are investigational — meaning they are being evaluated through carefully designed clinical research studies to better understand their safety and potential role in treating genetic hearing loss.

Clinical trials establish eligibility criteria to determine whether a child may qualify for hearing loss gene therapy. Because these approaches are still investigational, each trial uses specific inclusion and exclusion criteria to guide participation.

In general, eligibility for a clinical trial may include factors such as:

• A confirmed diagnosis of genetic hearing loss, often identified through a genetic evaluation or genetic hearing loss test
• A specific gene mutation associated with hearing loss
• A child's age and stage of development
• A child's hearing profile, including degree and type of hearing loss
• Overall health and medical history
• Previous treatments for hearing loss

These criteria help researchers better understand how gene therapy may work for different children and are designed to support participant safety throughout the study.

Children are typically referred for genetic testing through a multidisciplinary hearing evaluation that includes an otolaryngologist and genetic counseling. Families who would like to learn more about gene therapy for hearing loss can speak with their care team to better understand current research studies and whether participation in a clinical trial may be an option.

Gene therapy for hearing loss is still being studied and only works for very rare, specific genetic forms of hearing loss, which means it is not appropriate for most children with hearing loss. Like any new treatment, it has possible benefits and risks. These can vary based on the type of therapy, the genetic condition, and how the treatment is given.

Possible benefits may include:

• Improved hearing-related function for some children with specific genetic forms of hearing loss
• Treating the root cause of hearing loss, not just the symptoms

Researchers are still learning how well these treatments work, and each child may respond differently.

Possible risks may include:

• Immune reactions
• Problems with how the treatment is given
• Unintended effects on inner ear cells
• Side effects from the new genetic material
• Unexpected changes in how genes work

Children who participate in clinical trials are closely monitored during and after treatment so care teams can better understand the safety and outcomes of gene therapy.

Gene therapy is one of several options for children with hearing loss. Other options may include hearing aids, cochlear implants, sign language, or choosing no intervention.

Right now, doctors do not know if these treatments can fully restore hearing. Research is still ongoing, and some children may see improvements in hearing-related function, while others may not.

How well a child responds may depend on:

• Their specific genetic condition
• The type of treatment used
• Their age and hearing level at the time of treatment

Most studies are focused on whether hearing can improve, not on restoring normal hearing for every child. Results can be different for each child, and many questions remain. Families should talk with their child’s care team about what is known, what is still being studied, and what to expect when considering research studies.

Clinical trials advance gene therapy for hearing loss by answering important questions about safety, dosing, and how these approaches may affect hearing function in children with specific genetic forms of hearing loss.

Families who consider clinical trials for hearing loss gene therapy can expect a structured process. Care teams typically conduct genetic and hearing evaluations to confirm eligibility. Children who qualify will receive the investigational therapy and ongoing follow-up over time. Researchers use long-term monitoring to track outcomes, identify potential side effects, and better understand how gene therapy works in children to determine if the gene therapy can be offered as a part of routine care following the clinical trial.

Families interested in enrolling in pediatric hearing loss gene therapy trials should talk with specialists who are familiar with current research studies.

At Boston Children’s, we take a multidisciplinary approach to caring for children with genetic hearing loss. Specialists in audiology, otolaryngology, genetics and genomics, and clinical research work together to support each child’s care and help families understand the cause of hearing loss, along with available care and research options.

Families begin by meeting with a pediatric otolaryngologist for a comprehensive clinical evaluation to determine the type and cause of a child’s hearing loss and whether genetic testing is appropriate. Based on these findings, care teams guide families through next steps, including conversations about current research studies and whether gene therapy may be an option, while children continue to receive comprehensive hearing care.