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Genetic hearing loss happens when changes in certain genes affect how the hearing system develops and works. Learn more about the genetic factors contributing to hearing loss and the ongoing research on gene therapies aimed at improving outcomes for individuals who are deaf or hard of hearing. 

Cause of Genetic Hearing Loss

Genetic hearing loss occurs when changes in certain genes affect how the hearing system develops and works. Around half (50 - 60 percent) of hearing loss cases are found to be genetic. There’s thought to be hundreds of types of genetic hearing loss affecting different genes and different cells in the ear.  These changes, known as variants or mutations, can disrupt the formation of critical parts of the inner ear or interfere with the functioning of hair cells, which are essential for making sound into signals that the brain can understand. Depending on the specific gene involved, a person may be born with hearing loss (congenital) or develop it later in life. 

Inheritance Patterns

There are different ways hearing loss can be passed down in families. In most cases, a person with genetic hearing loss inherits two copies of a changed gene, one from each parent.  In this case, it is common for only one individual in the family to have hearing loss.  In other cases, a person inherits a single copy of a changed gene, which is sufficient to cause hearing loss.  In this case, it is common for multiple individuals and generations in the family to have hearing loss.  

Symptoms

The symptoms of genetic hearing loss can vary based on the underlying genetic cause.  Hearing loss can range from mild to profound and may be present since birth or develop later in life. Individuals may slowly lose their ability to hear, which can make it harder to communicate. Some individuals may also experience ringing in the ears (tinnitus) or have difficulty understanding speech, especially in noisy environments. 

Gene Therapy Approach

Gene therapy aims to correct or replace the genes that cause hearing loss. An example of a gene therapy approach being studied for hearing loss seeks to correct a non-working otoferlin gene, or OTOF gene for short. This gene produces otoferlin protein which is key for sounds to be transmitted from the ear to the brain. This approach uses a modified virus called a viral vector to deliver a working copy of a gene to the target cells. Scientists have learned how to remove the harmful parts of the virus from these viral vectors, ensuring that only the working gene reaches the target cells. The goal is to help hair cells and other parts of the hearing system work properly again, potentially reversing or significantly improving hearing loss.

This therapy may be given a few different ways. Examples of routes of administration that could be used to target the inner ear for otoferlin gene correction include:

Intra-Cochlear Injection (Directly to Inner Ear Administration)
This method delivers gene therapy directly to the cochlea through an injection. This approach involves injecting a gene therapy vector (such as an adeno-associated virus or AAV) directly into the cochlea, the spiral-shaped organ in the inner ear responsible for hearing.
Round Window Membrane Injection
The gene therapy is injected through a small membrane in the ear, called the round window, which connects the middle ear to the inner ear, allowing the treatment to reach the cochlea. The round window is a membrane-covered opening between the middle ear and the cochlea. Gene therapy can be administered via injection through the round window membrane, allowing the therapeutic agents to diffuse into the cochlea.
Intratympanic Injection (Middle Ear Administration)
In this method, the gene therapy vector is injected into the middle ear, where it can pass through natural openings (such as the round or oval windows) into the inner ear to help improve hearing function.

Gene therapy holds promise for addressing the root causes of genetic hearing loss. But at this time, each gene therapy approach being researched would not be one size fits all. This means for the over 250 underlying genetic causes, each one would likely need its own treatment designed.

Treatment Pipeline

The opportunity for more personalized care can be pursued through genetic testing, comprehensive physical and family history evaluation, and standard tests. This can help inform on a range of choices including: hearing aid, cochlear implant, listening and spoken language (LSL), sign language, other visual communication methods, or a gene therapy.  

Potential treatments for genetic hearing loss are currently under investigation, with some studies in clinical trials. Clinical trials are a required part of the research process for researchers and clinicians to understand how a treatment works in the human body and ensure it is safe and effective.  Before testing on people, researchers conduct preclinical studies in labs or with animals to see if a treatment is ready for human trials. Clinical trials for hearing loss evaluate the effects of new therapies on hearing function and overall quality of life for people with hearing loss. Ongoing clinical trials are crucial for testing new therapies and ensuring they meet the strict standards set by the Food and Drug Administration (FDA) before they can be made widely available.  To find out more about open clinical trials in the U.S. or around the world, you can visit the ASGCT Clinical Trials Finder and use the "diagnosis" filter to search for Hearing Loss studies. Alternatively, you can visit clinicaltrials.gov and use the “condition/disease” filter to search for related studies.

Participating in a Clinical Trial

The decision to participate in a clinical trial should be carefully considered, and it is a personal or family choice on which route to take.  It is essential for potential participants to understand the objectives of the study, as well as the risks and benefits associated with participation when weighing all options for hearing loss. Individuals or their caregivers should engage with healthcare professionals to discuss their options and gather information about ongoing clinical trials relevant to their specific condition. 

Eligibility

Eligibility for a clinical trial is based on specific criteria that determine who can or cannot participate.

These criteria help researchers ensure the gene therapy is working properly and to keep participants safe. These criteria may include factors such as age, physical ability, medical history, and more.

Speak with a healthcare professional or a member of the clinical trial research team to help determine if you or your child may be eligible for a clinical trial.

Risks

There are risks that need to be carefully considered before joining a clinical trial. A member of the research team should explain any potential risks and benefits to the affected individual or caregiver through the informed consent process.

Clinical trials are not a guaranteed cure and cannot guarantee beneficial results. There is always a chance that the investigational treatment may not work.

If a person is not satisfied with the outcome, the effects cannot be reversed and usually cannot receive another dose of the gene therapy.  However, research is underway to better understand whether re-dosing will be a possibility in the future.

Participating in a clinical trial may prevent an individual from future participation in other trials or receiving other types of treatments.

Gene therapy can be an alteration for the lifetime, so people should be aware that there could be long -term effects (both good or bad) that are not known at this time.

Benefits

Participating in a trial may offer many potential benefits compared to not receiving any form of intervention.

Gene therapy aims to be a one-time treatment with lasting positive effects to enable hearing for up to a lifetime. However, there is no guarantee.

If a gene therapy treatment (or another appropriate intervention for hearing loss) occurs earlier in the course of progression of the condition, the greater potential a child has to develop language skills.

Long-term follow up

It is the individual’s responsibility to comply with the long-term follow-up of a trial. The FDA guidelines require the clinical trial research team to monitor safety and potential long-term effects for years after giving a gene therapy.

Follow-up may require in-person appointments that vary in frequency and location, or completion of mailed packets with response forms.

The need for long-term data collection for a gene therapy trial can last up to 15 years—another reason to consider all outcomes and responsibilities that come with committing to a clinical trial.

There are a limited number of participants in trials, so a lack of attendance at follow-up appointments leads to not enough study data. This could negatively affect FDA approval of a new therapy and thereby limit access to the therapy by people who did not participate in the clinical trial.

Genetic testing and counseling can help inform individuals and families about inheritance patterns, potential treatment options, and progression of a condition.

Genetic Testing

Genetic testing is a diagnostic tool that may help individuals learn about the underlying genetic cause of their hearing loss.  When genetic testing results are available, genetic counseling may help in understanding how one's hearing loss could progress over time, the inheritance pattern and potential for other family members to have hearing loss, as well as available clinical trial options. At this time, eligibility for a clinical trial would require genetic testing to confirm if a person has the specific gene variant being targeted by that gene therapy. Gene therapy is not a one-size-fits-all. For the over 250 underlying genetic causes, each one would likely need its own treatment designed. The field is actively pursuing innovative ways to address this issue. 

Access

At present, there are no FDA-approved gene therapies specifically for genetic hearing loss, though research is progressing rapidly. The pathway to approval involves rigorous clinical testing to ensure safety and efficacy. Ongoing clinical trials are critical in advancing the understanding of genetic hearing loss and the development of new treatment options. Until such therapies are available, individuals are encouraged to stay informed about current research and available resources on hearing loss.

Stay Informed

There are many advocacy organizations to follow or get involved with. They work hard to fund research and advocate for individual and family needs. They are also a great way to connect with others affected by the condition if you are looking for support and advice.

Last Updated: 12/16/2024