N Engl J Med
Gene therapy restores hearing in children with inherited deafness
DB-OTO gene therapy restored functional hearing and normalized sensitivity in a subset of children, representing a major advance over device-based interventions. These results support further investigation and suggest gene therapy may offer curative potential for select forms of inherited deafness.
Study details: The phase 1/2 CHORD trial (NCT05788536) evaluated DB-OTO, an investigational adeno-associated virus (AAV)-based gene therapy, in 12 children (ages 10 months to 16 years) with profound congenital hearing loss due to biallelic mutations in the OTOF gene. DB-OTO delivers a full-length copy of the OTOF gene via intracochlear injection. Participants received the therapy in one or both ears and were followed for up to 72 weeks. Primary endpoint: behavioral pure-tone audiometry (PTA) ≤70 dB HL at 24 weeks; secondary endpoint: auditory brainstem response (ABR) ≤90 dB nHL.
Results: At 24 weeks, 9 of 12 children (75%) met both the PTA and ABR endpoints (95% confidence interval, 43-95; P=1.1×10-13 for both endpoints). Six could hear soft speech unaided, and three achieved average normal hearing sensitivity. No adverse events led to study discontinuation; 67 events were reported, all manageable.
Source:
Valayannopoulos V, et al; CHORD Study Group. (2025, October 12). N Engl J Med. DB-OTO Gene Therapy for Inherited Deafness. https://pubmed.ncbi.nlm.nih.gov/41085057/