Imagine a child born profoundly deaf hearing their parent’s voice for the first time. Thanks to groundbreaking gene therapy research, this is no longer science fiction. A clinical trial known as CHORD is investigating whether gene therapy can restore hearing in children with a specific genetic form of deafness caused by mutations in the OTOF (otoferlin) gene. Early results have been remarkable, with many children gaining significant hearing ability and some achieving hearing levels within the normal range.
Understanding OTOF-Related Hearing Loss
The OTOF gene provides instructions for making otoferlin, a protein that helps sensory hair cells in the cochlea transmit sound signals to the auditory nerve. Children who inherit faulty copies of the gene from both parents are born with profound hearing loss because sound signals cannot be effectively transmitted to the brain. Importantly, the structure of the inner ear remains largely intact, making this condition an ideal target for gene therapy. Until now, the primary treatment option has been a cochlear implant, which bypasses the faulty signalling pathway and directly stimulates the auditory nerve. While cochlear implants provide life-changing access to sound, they do not restore natural hearing. Gene therapy aims to address the underlying cause of hearing loss rather than bypassing it.
What Is the CHORD Trial?
The CHORD trial is a Phase 1/2 clinical study evaluating an experimental gene therapy called DB-OTO, developed by Decibel Therapeutics (acquired by Regeneron). The treatment uses a modified adeno-associated virus (AAV) to deliver a healthy copy of the OTOF gene directly into the cochlea. Once delivered, the goal is for the hair cells to begin producing otoferlin, restoring normal communication between the ear and the auditory nerve. The procedure is performed under general anaesthetic and is similar to cochlear implant surgery. Some participants have received a cochlear implant in one ear and gene therapy in the other, allowing researchers to compare outcomes while ensuring children continue to receive established treatment. The international trial has enrolled children ranging from infancy through adolescence across sites in the United States, United Kingdom, Spain and Germany. Researchers are assessing both safety and hearing outcomes using behavioural hearing tests and objective measures such as Auditory Brainstem Response (ABR) testing.
Early Results Have Been Extraordinary
The results reported to date have generated significant excitement throughout the hearing healthcare community.
Of the first 12 children treated:
- 11 demonstrated clinically meaningful improvements in hearing.
- Nine achieved hearing thresholds of 70 dB or better within six months.
- Three reached hearing levels within the normal range for their age.
- Several others achieved near-normal hearing.
In some cases, children who were previously unable to respond to any sound began responding to speech and environmental sounds within weeks of treatment. Researchers also observed continued improvements over time, suggesting the therapy’s benefits may increase as the auditory system adapts.
One widely publicised participant, a young girl from the UK, reportedly developed hearing in her treated ear sufficient to function without relying on her cochlear implant. Stories such as these highlight the profound impact the treatment could have on communication, language development and quality of life.
Is It Safe?
Safety has been the primary focus of the early trial phases. So far, no serious treatment-related adverse events have been reported. Some participants experienced temporary dizziness or nausea following surgery, which resolved within days. A small number experienced minor fluctuations in hearing that improved with treatment and monitoring.
Because the gene therapy is delivered directly into the cochlea, exposure to the rest of the body is limited, reducing the risk of systemic side effects. Researchers continue to monitor participants closely to assess long-term safety and durability of the hearing improvements.
Why Genetic Testing Matters
One of the most important messages emerging from this research is the growing importance of genetic testing for children diagnosed with hearing loss. Historically, identifying the specific genetic cause of hearing loss often had limited impact on treatment decisions. Today, precision medicine is changing that landscape. Knowing a child’s genetic diagnosis may help determine eligibility for future gene therapies and clinical trials.
Australian researchers are already contributing to this work. Studies investigating the natural history of OTOF-related hearing loss are helping establish the foundations needed for future gene therapy programs and clinical trials within Australia.
What Could This Mean for the Future?
The success of the CHORD trial represents a potential shift in hearing healthcare.
For decades, treatment has focused on managing hearing loss through hearing aids and cochlear implants. Gene therapy introduces the possibility of correcting some forms of hearing loss at their genetic source. This approach will not replace hearing aids or cochlear implants. Many people with hearing loss will continue to rely on these technologies, and not all forms of hearing loss are suitable for gene therapy. However, for children with specific genetic conditions such as OTOF-related deafness, gene therapy may eventually provide an alternative pathway to hearing development. Researchers are already exploring gene therapies for other forms of inherited hearing loss, including conditions caused by mutations in the GJB2 (Connexin 26) gene, one of the most common causes of congenital deafness worldwide.
Looking Ahead
Although DB-OTO remains an investigational treatment, the early results suggest that gene therapy may become the first treatment capable of restoring hearing in some children with genetic deafness. Regulatory approval is still required, and questions remain about long-term outcomes, accessibility and cost. Nevertheless, the progress seen so far marks an important milestone in hearing healthcare. For families affected by genetic hearing loss, these developments offer something that has rarely existed before: the possibility of treating the underlying cause rather than simply managing the consequences. If future studies continue to confirm these findings, gene therapy may become one of the most significant advances in audiology since the development of the cochlear implant.
References
Contemporary Pediatrics. (2025). Gene therapy DB-OTO shows hearing improvements in children with otoferlin-related hearing loss.
Millichap, J., et al. (2025). Gene Therapy for OTOF-Mediated Hearing Loss. New England Journal of Medicine, 393(17), 1591–1602.
Murdoch Children’s Research Institute. (2025). Natural history study of otoferlin-related hearing loss.
Regeneron Pharmaceuticals. (2025). CHORD trial update: DB-OTO gene therapy demonstrates meaningful hearing improvements in children with otoferlin-related hearing loss.
The Audiology Place. (2025). Gene therapy breakthrough offers hope for children with genetic hearing loss.
University of Melbourne Pursuit. (2021). The Australian invention that transformed hearing: The cochlear implant.
ABC News UK. (2025). Toddler gains hearing after experimental gene therapy treatment.
