Gene therapy breakthroughs are offering hope to those with hereditary deafness, as researchers successfully restore hearing in children born deaf and pave the way for treating various genetic hearing disorders.
At a Glance
- Clinical trials in Shanghai, Italy, and the U.S. have successfully restored hearing in children with congenital deafness caused by mutations in the OTOF gene
- The gene therapy involves injecting functioning copies of genes into the inner ear using adeno-associated virus (AAV) vectors
- Treated children have shown dramatic improvements, including the ability to hear voices, localize sounds, and in some cases, appreciate music
- Researchers are now expanding trials internationally and developing treatments for other forms of genetic hearing loss
- Over 1.5 billion people worldwide suffer from hearing loss, with genetic factors causing 30 million cases in children
Groundbreaking Results in Children Born Deaf
A gene therapy trial in Shanghai has successfully restored hearing in both ears of five children with DFNB9, a form of autosomal recessive deafness caused by mutations in the otoferlin (OTOF) gene. This landmark achievement represents the first clinical trial to provide gene therapy for this type of inherited deafness to both ears, setting a new standard in treatment approaches. The therapy involves delivering functioning copies of the OTOF transgene directly into the inner ears using adeno-associated virus (AAV) vectors.
The results have been remarkable, with all five children showing significant hearing recovery. Beyond simply detecting sounds, the children demonstrated improved sound source localization and speech perception in noisy environments – critical abilities for navigating everyday life. No serious adverse events were reported, and some children even gained the ability to appreciate music, opening up an entirely new sensory world for them.
— ValeriusX (@BioMayflower) February 19, 2025
International Progress and Innovative Approaches
The success in Shanghai is not an isolated achievement. An Italian research team developed an innovative gene therapy technique that enabled an 11-year-old boy with congenital deafness to hear for the first time. Their approach tackled a significant technical challenge: the OTOF gene is too large to fit into a single AAV vector. The solution involved splitting the gene into two parts carried by separate viral vectors, which then reassemble inside the patient’s cells.
Four months after surgery, the boy’s hearing improved from complete deafness to mild hearing loss, allowing him to detect voices and ambient sounds. This dual-vector approach opens possibilities for treating other genetic conditions where the therapeutic gene exceeds standard vector capacity limits. Similar success was reported at the Children’s Hospital of Philadelphia, which performed the first U.S. gene therapy procedure for OTOF-mediated hearing loss on an eleven-year-old patient.
Expanding Treatment Horizons
The scope of genetic hearing loss research is expanding beyond OTOF mutations. Japanese researchers have developed a revolutionary gene therapy targeting syndromic hearing loss caused by mutations in the GJB2 gene, which is responsible for a significant percentage of hereditary hearing loss cases. Their approach uses a specially designed adeno-associated virus vector (AAV-Sia6e) to target inner ear hair cells. The technique has successfully restored normal gap junction formation in cultured human cells with the GJB2 R75W mutation.
The human impact of these scientific advances is perhaps best illustrated by the story of toddler Opal Sandy, born with total deafness due to a fault in the OTOF gene. After receiving gene therapy through the international Chord trial, conducted in the U.S., Britain, and Spain, Opal can now hear. This trial represents a collaborative effort to make these groundbreaking treatments available to children worldwide affected by congenital deafness.
Future Directions and Broader Impact
Hearing loss affects over 1.5 billion people globally, with genetic factors causing approximately 30 million cases in children. The OTOF mutation responsible for DFNB9 affects between 2 to 8 percent of genetic deafness cases from birth. While current trials focus on specific genetic mutations, researchers aim to expand their work to address other forms of genetic hearing loss.
These breakthroughs provide proof-of-concept that laboratory animal research can successfully translate to human treatments. As more patients of different ages receive these gene therapies, researchers will gather vital data on hearing improvement sustainability and long-term outcomes. For the millions of people worldwide affected by genetic hearing loss, these developments represent not just scientific achievements but life-changing opportunities to experience sound for the first time or regain lost hearing.
