Researchers have developed a gene therapy called DB-OTO that delivers a protein crucial for hearing to children with inherited deafness caused by a genetic deficiency. The treatment, which involves injecting the gene into the inner ear, improved hearing in 75% of the participants who received it.
DB-OTO is a dual adeno-associated virus 1 gene therapy that targets the sensory hair cells of the ear and delivers human OTOF complementary DNA, which encodes the protein otoferlin. This protein is critical for synaptic transmission by the sensory hair cells, allowing them to transmit sound signals to the brain.
In an open-label study, 12 children with severe hearing loss due to genetic variants of the OTOF gene received DB-OTO treatment in one or both ears. The primary outcome measure was an average threshold on behavioral pure-tone audiometry (PTA) at week 24, which is a clinical standard that avoids cochlear implantation and enables natural acoustic hearing.
The study found that 9 out of 12 participants met the primary end point of having an average PTA threshold of 70 dB HL or less at week 24. Six participants could hear soft speech without assistive devices, and three had average normal hearing sensitivity.
While the treatment was generally safe, 67 adverse events occurred during or after treatment. The study authors concluded that DB-OTO gene therapy improved hearing in patients with OTOF-related deafness, enabling natural acoustic hearing and normalizing hearing sensitivity in some participants.
Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2400521