A New Hope for Childhood Deafness

Cassidy DeMasi

Dr. Barbato

12/7/2025

                                                      A New Hope for Childhood Deafness

The OTOF gene allows the inner ear send sound signals to the brain. We first learn about whether this gene is functioning appropriately when a child is first born, because we learn that they fail their newborn hearing test. This is because when this gene has a mutation, the ear can hear sound but can’t send the signal correctly. This causes auditory neuropathy. It is typically inherited from both parents and is often best treated with a cochlear implant. However, cochlear implants require surgery, and the last thing that a parent wants their young kid to go through is surgery. 

However, there is a new genetic treatment on the market presented by the University of Cincinnati. The study states, "The treatment, which targets a mutation in the otoferlin (OTOF) gene, has been effective in most of the tested children. The rare mutation causes hearing loss in an estimated 20 to 50 babies born in the U.S. each year. Deafness linked to OTOF mutations is a type of auditory neuropathy, a spectrum of disorders in which the inner ear can detect sound but struggles sending that information to the brain," (Burgasser, 2025) This discovery brings new hope to families that just want their children to hear their voice for the first time. It also contributes to discoveries in new findings for potentially curing genetic deafness.

Resources 

Burgasser, M. (2025, December 8). The gene therapy poised to rewrite childhood deafness. UC News. https://www.uc.edu/news/articles/2025/12/the-gene-therapy-poised-to-rewrite-childhood-deafness.html

OTOF otoferlin [Homo sapiens (human)] - Gene - NCBI. (n.d.). Www.ncbi.nlm.nih.gov. https://www.ncbi.nlm.nih.gov/gene/9381

Gene Therapy Helping Deaf Children

 A new test has reported that the hearing of five deaf children has been restored using gene therapy. The children were all born with DFNB9, an inherited disease which is the result of mutations in the OTOF gene. The children received functioning versions of the OTOF gene via injections of a virus. In 2022 this gene therapy was proven to work when six patients received it and had some successful recovery of hearing. Although in both trials no side effects were observed, researchers believe that a second dose might cause a strong immune response.

https://www.usnews.com/news/health-news/articles/2024-06-05/gene-therapy-in-both-ears-restores-hearing-to-babies-born-deaf

https://masseyeandear.org/news/press-releases/2024/06/gene-therapy-trial-shows-restored-hearing-and-speech-in-children-born-deaf

Gene Therapy Brings Hearing to Kids With Congenital Deafness

    The article titled “Gene Therapy Brings Hearing to Kids With Congenital Deafness” reports that gene therapy is being tested to bring back the hearing of children with congenital deafness. This is done by injecting the protein responsible for transferring sound singles called otoferlin, into the inner ear of six deaf children, and studies have found that they have experienced hearing within approximately six months of the injection. A lack of otoferlin is typically caused by a gene mutation that ends up making people deaf from birth. Otoferlin correction is a groundbreaking study because it is the first treatment in almost 60 years for deafness. Gene therapy for deaf children has also correlated to better speech patterns and allowed children to carry out thorough conversations. 

    I think this article is great and brings a lot of meaningful insight into how long there has been no treatment or cure for congenital deafness. It shows that research with gene therapy is also advancing to a point where researchers are making groundbreaking discoveries for new treatments for different disabilities or diseases. 

Reversing Hearing Loss

                                                         Reversing Hearing Loss

Hearing loss is a very common defect to many people no matter the age. There are many people who have been born with a hearing defect and have only used hearing aids and implants, those only work so well. Scientists have believed to find a way to improve your hearing through the genes we have. 

A recent study that they had, they saw there was ​​a gene associated with early onset deafness reversed hearing loss in mice and they hope they can eventually use this information to apply it to humans with hearing loss. They believe that this can one day lead to a solution to people with hearing issues due to genetic issues. 

To study how genetic hearing loss occurs, Steel and the other members of her team mutated spinster homolog 2 Spns2, a gene associated with early onset hearing loss and subsequent deficiency in endocochlear potential (EP). What that does is it basically works as a batter for the inner ear.

In my opinion this is a very beneficial study that they are doing regarding genetics. Many people suffer from hearing loss and so do their parents, which can lead to be a genetic hearing defect. That can help many of those people as well as people born with hearing defects that are due to genetic mutation, or lack of a gene.

Links:

https://www.the-scientist.com/magazine-issue/reversing-hearing-loss-71423https://news.mit.edu/2022/frequency-therapeutics-hearing-regeneration-0329

A Genetic Patch that Eliminates Hearing Problems associated with the DFNA9 Gene

 

According to the researchers at the Radboud University, a genetic patch can eliminate hearing problems associated with the DFNA9 gene. Usually, the mutation in the DFNA9 gene causes deafness from birth. In some cases, hearing problems can occur after forty years. If inherited a mutated copy of the gene, then hearing problems will develop later in life. If inherited two normal copies of the gene, then that person will have normal hearing. The genetic patch, known as antisense oligonucleotide, works by developing a small piece of RNA that binds to the RNA messenger from the muted DFNA9 gene. This stops the production of the mutant DFNA9 protein. Adding the genetic patch would prevent further damage to the ear. Another option to treat problems associated with the DFNA9 gene is to turn it off. This would also stop the production of the mutant DFNA9 protein.  

Articles:

https://neurosciencenews.com/genetic-patch-deafness-17935/

https://www.cell.com/molecular-therapy-family/nucleic-acids/pdf/S2162-2531(21)00068-8.pdf?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2162253121000688%3Fshowall%3Dtrue

More Clues to the Genes Behind Hearing Loss

Article: https://www.usnews.com/news/health-news/articles/2020-07-16/more-clues-to-the-genes-behind-hearing-loss 

Related Article: https://www.technologynetworks.com/genomics/news/common-genetic-variant-identified-as-frequent-cause-of-deafness-337136

    This past month, Dutch scientists have been able to research and identify a common genetic variant that can cause deafness. There are about 118 genes identified to be linked to deafness, most of these exressed at birth or early childhood. A study of about 200 people was conducted and it was found that a missing section of the RIPOR2 gene was detected in 20 of 23 families with inherited deafness. With more studies, it was found that the gene variant could be found in those with hearing loss and those with no hearing loss yet. It is predicted that the gene variant is present in more than 43,000 people who can either be present with hearing loss or are at risk. Identifying this gene is going to open up doors to making a targeted gene therapy. 

Deafness Gene GJB2 Edited in Human Eggs

Denis Rebrikov is a Russian biologist that started editing the GJB2 gene, associated with deafness, in human eggs donated by women who can hear. The GJB2 gene produces a protein in gap junctions, the channels that help move chemical signals like potassium between cells, including in the inner ear. Rebrikov told Science that he plans to do extensive safety checks before seeking approval to implant an edited embryo. First, he wants to sequence the entire genomes of each parent to get a baseline for assessing off-target mutations in their edited embryos. He then wants to stimulate the woman’s ovaries, obtain about 20 eggs, fertilize them with her partner’s sperm, and finally add the mutation fixing CRISPR. He’ll grow these embryos for 5 days, at which point they will have about 250 cells and be in the blastocyst stage. Then he will do repeated rounds of whole-genome sequencing of 10 of these blastocysts, which will reveal all mutations that differ from the genomes of the parents. he will move to the next stage with the remaining edited embryos: a preimplantation test, then he will check the cells for many types of genetic defects and for mosaicism for the CRISPR edit.

He does not plan to create gene-edited babies just yet. He is studying normal copies of GJB2 to better understand potentially harmful mutations associated with using CRISPR. His eventual goal is to edit the eggs of deaf women in order to allow deaf couples with GJB2 mutations to have children with functioning copies of the gene and typical hearing. The experiment is similar to work done by researcher He Jiankui, who announced last year that he had created CRISPR-edited twin babies whose genomes were modified in hopes of making them resistant to HIV.



Article: https://www.the-scientist.com/news-opinion/deafness-gene-gjb2-edited-in-human-eggs-66600

Related Article: https://www.sciencemag.org/news/2019/10/embattled-russian-scientist-sharpens-plans-create-gene-edited-babies

38 New Genes related to hearing loss found in mice

In a recent study done at the Wellcome Sanger Institute discovered 38 new genes in mutant mice that are related to hearing loss.  Hearing loss is very prevalent in our society, with many people experiencing deteriorating hearing as they age. The study done on 1,211 mutant mice revealed 38 new genes related to hearing loss that were not known before. Out of the 38 found, 11 of the genes can be linked significantly to the hearing ability in the UK population. One of the genes, SPNS2, is linked to childhood deafness.  The studies done show that hearing disorders are varied and can involve as many genes as 1000. Therefore there will not be an end all cure to hearing loss, but the new research is a big step forward in helping prevent hearing loss. The research can even be used to just slow down the rate at which people lose their hearing ability.

This new research is very important for the fact that it can help prevent hearing loss as we age. Without hearing, someone's social life can be dramatically effected. Without the ability to hear everyday activities can become strenuous and tedious. Being able to push back, or even prevent hearing loss with age would be very beneficial to us all.

Gene Therapy Reverses Congential Deafness in Mice

Scientists from the Institut Pasteur, Inserm, CNRS, and many other universities have collaborated to restore hearing in adult mice of DFNB9 deafness. Someone who has DFNB9 deafness are deficient in the gene coding for otoferlin, which is a protein that transmits sound information. The scientists restored the auditory synapase threshold, which receives the sound information, to a near-normal level. DFNB9 deafness is the same for humans and mice, that is why mice are used as models to test the efficiency of gene therapy.  Scientists came up with a Adeno-associated virus (AAV) approach, known as the dual AAV strategy becuase it uses two different recombinant vecotrs. An intracochlear injection of the vector pair was injected in adult mice to reconstruct the otoferlin coding region, resulting to a long-term restoration of otoferlin. With these findings, scientists can help individuals with DFNB9 deafness, to restore their hearing and also discover other types of deafness and hopefully be able to cure the other types of deafness.

 

I found this article to be interesting because a small percentage of individuals suffer with DFNB9 deafness since the prenatal stages, so they are born with it. It is interesting how scientists were able to use mice as a model for DFNB9 deafness since humans and mice express the mutation the same way. The scientists were able to restore deafness in the mice models for log-term and hopefully, it will restore hearing for humans long-term as well. Also, with these findings, scientists can also discover other types of deafnesses associated with humans and mice and hopefully find a cure for those other types of deafnesses.

Mutant gene discovered that can cause deafness

          The Scripps Research Institute discovered that one specific gene is responsible for deafness, and is essential to our hearing. Our ears convert the mechanical sound waves into electric signals, so our brain can process it. When the sound wave enters the ear the uneven ends, or the stereocilia, of the inner ear's hair cells are pushed back. This movement causes tension in the strings of the proteins connecting the stereocilia, which sends signals to the brain through ion channels that run through the tips of the hair cell bundles (medicalnewstoday.com). This process is called mechanotransduction, which still poses many questions to researchers. They still were not sure how the signals were passed along the tip links to the ion channels.  To track this mystery, they did tests with thousands of different genes to see which gene affected mechanotransduction. After six months of research, they finally found a gene with the protein TMIE, which interacts with the tip links and connects them to the ion channel. Researchers were already aware that tmie can cause deafness, but they weren't sure how. After doing this research, they did a study in which they bred mice that lacked the gene tmie, and these mice were completely deaf. In their second experiment, they reintroduced tmie in the mice that have been bred deaf since birth. They found that the electrical signals were restored, which means the mice were able to hear again. In my opinion, the fact that they were able to track deafness to a specific gene is amazing to me. Hopefully, with being able to restore the hearing in mice, they can come up with ways to restore hearing in humans who have this specific gene mutation.


Original article: http://www.medicalnewstoday.com/releases/285938.php
Related article: http://www.medicalnewstoday.com/articles/249285.php

Gene Mutation Linked to Deafness

Recently scientists at The Scripps Research Institute (TSRI) have discovered how there is one gene  in particular essential to hearing. By studying this gene they believe they have uncovered a new cause of deafness. Tmie is the name of the gene believed to be held responsible. Mutations in this gene can cause deafness from birth. After reintroducing the gene to mice and seeing promising results towards restoring hearing,  Professor Ulrich Müller says "This raises hopes that we could, in principle, use gene-therapy approaches to restore function in hair cells and thus develop new treatment options for hearing loss". Mechanotransduction is the process that allows us to hear. Mechanical sounds waves are converted into electrical signals for the brain. The signals are passed from fine hairs within the eye along ion channels to the brain. After 6 months of studying genes, the team eventually found the protein TMIE which interacted with the top link protein and acts as the connections the links to the ion channel. This study will hopefully open the door towards new genetic gene replacement therapy and the curing of deafness in certain individuals.

http://www.medicalnewstoday.com/releases/285938.php

Mutant Gene that Causes Deafness Discovered

       Researchers have recently discovered a mutant gene called Tmie that can cause deafness from birth. Scientist were then able to reintroduce the gene in mice and restore hearing, instilling new confidence that with the identification of this gene, gene therapy can be used to restore hearing in humans.

      The scientists identified the Tmie gene by studying the process of hearing, which involves mechanotransduction (the process of converting mechanical force into electrical activity). Researchers specifically looked for how signals were passed along tip link proteins and to the ion channels (essentially electric signals). They eventually found the Tmie gene, whose protein TMIE interacts with tip link proteins a connects the tip links to a piece of machinery near the ion channel.

    Researchers then bred a population of mice that lacked the gene. They studied these mice and found that without the Tmie gene, no electrical signal could be invoked in the hair cells after stimulation, meaning the mechanotransduction current is totally gone and the mice were deaf. In a second part of the experiment, researchers reintroduced Tmie into mice that had been deaf since birth and found that hearing was restored. This new breakthrough means gene therapy may be able to be used to restore hearing in humans and even possibly knock out deafness entirely in the future. 

 Article

Say What? Deaf No More

In the near future there may be a new solution to hearing loss.  Scientists believe that instead of the usual cochlear implants in patients that are deaf or hard of hearing, they may soon be able to achieve significant success using gene therapy.

Gene therapy is where DNA or RNA is transported by a carrier  to other cells to provide instructions for replacing damaged genes.  This is difficult because the carrier must be able to get the genetic material through the membranes protecting these damaged cells.However, chitosan nanoparticles have recently been used as a carrier and they have shown the ability to safely carry the genetic material to the desired destinations.  Chitosan is produced from shrimp shells and does a good job keeping DNA and RNA's large molecules in order to transport them.  So far Chitosan has been able to transport this genetic material successfully to the hair in the inner ear of guinea pigs, but it is not yet proven to work in humans.

Gene Mutation for Deafness Also Responsible for Sensitivity to Some Types of Touch

Since 1997, it has been known that mutations to the KCNQ4 K+ channel, a potassium ion pathway only found in three places: 1) on sound-detecting hair cells in the inner ear that leads from the external environment to neurons, 2) a part of the brain stem involved in hearing, and 3) neurons in the skin that help us to sense touch on mutations, lead to progressive deafness. Now a new study on mutations in this same pathway suggests that they also cause heightened sensitivity in skin. The researchers found that in both mice and humans, they disrupt the channel’s buffering ability, which would normally prevent neurons from becoming over-stimulated as stimuli is passed from the channel to the neurons. As this ability to buffer decreases in the inner ear, the hair cells slowly die, which leads to deafness.

[caption id="attachment_3237" align="aligncenter" width="519" caption="The KCNQ4 gene is located on base pair 41,249,683 to base pair 41,306,123 on the short (p) arm of chromosome 1 at position 34, as shown here."][/caption]

Additionally, the team discovered that in mice and human families with this gene mutation, the channel only appeared in neurons in skin that were sensitive to low level vibrations, and that humans with the mutation are better able to discern the subtle differences between various soft materials because of this. They also found that this heightened sensitivity to these types of touch was actually in existence before they went blind, meaning that this sensitivity was not a subsequent adaptation made by the body. Finally, they noted that this particular gene mutation in the KCNQ4 channel is one of many gene mutations that can cause deafness, leading them to conclude that not all those who develop progressive deafness will necessarily develop this type of sensitivity to touch.

The idea that certain traits can be inherited simultaneously (in this case, progressive deafness and increased skin sensitivity) is not a new one – a very common example is sex-linked disorders. However, genetic mutations such as this one are still very mysterious in nature simply due to the fact that there are many similar channels, such as the KCNQ1 channel, that have yet to be studied extensively.

The abstract of the original research article can be found here.