Deafness Gene Therapy Team Publishes World's First Gene Therapy vs Cochlear Implant Cohort Study

Background

Congenital deafness caused by mutations in the OTOF gene disrupts the production of otoferlin, a protein required for communication between inner hair cells in the cochlea and the auditory nerve. This results in severe to profound sensorineural hearing loss present from birth. For decades, cochlear implantation has served as the primary intervention for such profound hearing loss.

What was achieved

In a nonblind cohort study conducted from December 2022 to November 2024 at the Eye & ENT Hospital of Fudan University, 11 patients (mean age 3.7 years) received OTOF-targeted gene therapy while 61 matched patients (mean age 1.9 years) received cochlear implants, for a total of 72 individuals. Results published online July 21, 2025 in JAMA Neurology (and appearing in the September 2025 issue) showed that among nine gene therapy patients completing 12-month follow-up, auditory brainstem response thresholds improved from greater than 95.0 dB nHL to a mean of 54.8 (15.9) dB nHL.

Gene therapy patients achieved higher median IT-MAIS/MAIS scores at 6 months (31.0 vs 23.5; P=.01) and 12 months (32.0 vs 28.0; P=.007) compared with the cochlear implant group. They also exhibited shorter mismatch negativity latencies at 6 months. In bimodal comparisons at 12 months, gene therapy demonstrated advantages in speech perception in a noisy environment (median -1.0 vs 5.3 dB SPL) and singing in-tune rates for music perception (66.6% vs 37.1%; P=.04). The study, led by Yilai Shu with contributions from Huawei Li, Xiaoting Cheng and others, is described as the first direct cohort comparison of gene therapy versus cochlear implantation for congenital deafness. Gene therapy patients showed stable hearing recovery with more rapid improvements and outperformed in speech-in-noise and music perception.

How it works

OTOF-related deafness occurs because the mutated gene prevents inner hair cells from properly releasing neurotransmitters in response to sound, even though many cochlear structures remain intact. The gene therapy uses an adeno-associated virus (AAV) vector carrying a functional version of the human OTOF gene. Under general anesthesia, clinicians perform a minimally invasive transcanal endoscopic procedure to inject the vector through the round window membrane directly into the inner ear. Once inside target cells, the gene enables production of functional otoferlin protein, restoring natural synaptic transmission and acoustic hearing.

By comparison, cochlear implantation involves surgical placement of an electrode array into the cochlea to deliver electrical signals that directly stimulate the auditory nerve, bypassing the hair cells and synapse. Study outcomes were evaluated using tools including the IT-MAIS/MAIS scales, speech recognition tests in noise, music perception tasks such as singing in-tune rate, parental questionnaires, and objective measures such as auditory brainstem response thresholds and mismatch negativity latencies that reflect auditory cortex processing.

What it means for international patients

The comparative evidence from this cohort study indicates that gene therapy for OTOF-related congenital deafness may provide stable natural hearing recovery with advantages over cochlear implantation in speed of auditory and speech gains as well as performance in noisy environments and music perception. The Eye & ENT Hospital of Fudan University maintains an International Medical Center and provides guidance for foreign passport holders, including passport-linked electronic patient cards for registration, appointments, and reports via its official website and WeChat platform.

Professional interpreters for English, French, and Korean are available, along with cooperation with certain international commercial insurers for direct settlement. International patients or families considering evaluation for gene therapy or related deafness treatments must confirm their specific genetic diagnosis, current program availability, and personal eligibility criteria directly with the hospital, as these advanced interventions require specialized assessment and may be subject to ongoing clinical or regulatory frameworks.

About the hospital

Located in Shanghai with multiple campuses including the main Fenyang Road site in Xuhui District and a Pudong campus, the Eye & ENT Hospital of Fudan University is a Grade 3 Class A (tertiary A) public specialty teaching hospital affiliated with the Shanghai Medical College of Fudan University. Founded in 1952, it integrates clinical care, teaching, and research exclusively in ophthalmology and otorhinolaryngology (ENT), both designated as national key disciplines and national key clinical specialties by Chinese authorities.

The hospital's otorhinolaryngology department has ranked first in national hospital reputation surveys for over a decade, with ophthalmology consistently ranked among the top three. It operates with several hundred beds across sites, sees a high volume of patients from across China and abroad, and includes dedicated support for international patients through its International Medical Center.