"I heard it, a buzzing sound!" At the Chegu Campus of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, the boy Yangyang (pseudonym) said joyfully during a hearing test, while his mother beside him wept with joy.

On the 21st, Union Hospital announced that its Department of Otorhinolaryngology, Head and Neck Surgery team had completed a gene therapy case for hereditary deafness, significantly improving the hearing of a deaf child. This clinical trial is the first of its kind in Central China and will help patients deafened by OTOF gene mutations to set aside "external devices" such as cochlear implants and hearing aids, restore their own hearing, and listen to the real sounds of the world. Professor Xiao Hongjun, Director of the Department of Otorhinolaryngology, Head and Neck Surgery at Union Hospital, stated that this gene technology opens a new direction for deafness treatment and brings new hope to patients with other congenital deafness.

Long accompanied by a cochlear implant, the boy longed to "hear better"

Yangyang (pseudonym), 15, comes from a rural area in Shaanxi Province and has suffered from profound congenital deafness since birth, with both ears nearly completely deaf. Because newborn hearing screening was missed, his parents only discovered his slow response to sound when he was nearly 1 year old. The local hospital diagnosed the child with deaf-mutism and arranged for him to wear a hearing aid for half a year, but the results were poor. The family of three traveled to multiple hospitals in Xi'an and Beijing, and at age 3 Yangyang underwent cochlear implant surgery and began speech rehabilitation training.

However, Yangyang's hearing was far from comparable to that of normal children. The reporter learned that the number of channels in a cochlear implant is limited; it may divide natural sounds into a dozen or so channels or twenty-odd channels, whereas the human body has thousands of hair cells to receive sound. Therefore, the fineness and richness of sound captured by a cochlear implant cannot be compared with real sound.

Yangyang's parents longed for a better treatment. They made inquiries everywhere and learned that the otolaryngology department of Union Hospital was conducting a clinical trial of gene therapy for children with congenital deafness. In early January 2024, the couple came to the hospital with their child, clinging to a glimmer of hope.

The deaf son raised his hand again and again to "hear," and his mother shed tears

According to the diagnosis at Union Hospital, Yangyang's condition was hereditary deafness caused by an OTOF gene mutation. OTOF gene mutation is one of the main causes of auditory neuropathy, which occurs mostly in infants, young children, and adolescents. After genetic testing and comprehensive analysis, the team determined that Yangyang was suitable for the hospital's ongoing clinical trial on hereditary deafness, and his parents agreed to "be the first to eat the crab" together.

"Let the child hear real sounds with his own ears one day sooner." This was the shared hope of the medical team and the parents. On February 9, the morning of Chinese New Year's Eve, Yangyang was taken into the operating room at the Chegu Campus of Union Hospital.

The team of Professor Xiao Hongjun and Professor Sun Yu from the Department of Otorhinolaryngology, Head and Neck Surgery worked closely with the anesthesiology department and operating room staff. The cochlea is located deep in the brain, and the team ingeniously created a pathway to precisely inject the gene drug into Yangyang's inner ear through the round window membrane.

"That's a car horn." On the third day after surgery, Yangyang removed his cochlear implant and, relying on his left ear—which had just received treatment—heard sound, and was overjoyed. Professor Sun Yu explained that hearing was re-examined on the seventh day after surgery. Yangyang's left ear hearing had improved significantly. During the hearing test, he raised his hand whenever he heard a sound as instructed. His mother, watching through the glass as her child raised his hand again and again, shed tears of joy.

From "0" to "1": gene therapy opens a new path for hereditary deafness

It is understood that about 30,000 deaf children are born in China each year, and more than 60% of deafness is related to genetic factors. Hereditary deafness is the main pathogenic factor causing prelingual hearing loss.

Professor Xiao Hongjun introduced that among infants and young children with auditory neuropathy in China, the incidence of deafness caused by OTOF gene mutations is as high as 41%. The OTOF gene is mainly involved in the release of neurotransmitters from synaptic vesicles of inner hair cells in the cochlea, enabling the brain to perceive sound. The lack of otoferlin expression in inner hair cells prevents sound stimulus signals from being properly transmitted to the auditory neural pathway, and the person cannot "hear" sound or form speech.

Apart from cochlear implants, there is no effective therapeutic drug worldwide. Gene therapy for hereditary deafness is a breakthrough from "0" to "1," and only a few teams at home and abroad are exploring this field. Professor Sun Yu introduced that adeno-associated virus (AAV) is currently the most commonly used gene therapy delivery vector, but the OTOF gene exceeds the loading capacity of a single AAV. "One vehicle can't move it; two vehicles are needed to move it together. After the drug is injected into the human body, these two vehicles need to merge to form a complete gene and take effect." To overcome the challenge of delivering large genes into the inner ear, the hereditary deafness gene research team used a dual-vector AAV delivery system, in which two AAV vectors carry the OTOF gene, restoring protein expression in an OTOF deafness animal model and thereby significantly improving hearing.

It is understood that Yangyang is currently the oldest patient in the world to undergo gene therapy for deafness. The Department of Otorhinolaryngology, Head and Neck Surgery at Union Hospital is the fourth unit in the world to carry out inner ear gene therapy for hereditary deafness and ranks first in Central China.