Autosomal recessive deafness 9 (DFNB9) is a congenital hearing disorder caused by mutations in the OTOF gene, leading to severe-to-complete bilateral hearing loss. However, no pharmacological treatments currently exist for this condition. To address this gap, a clinical study evaluated the safety and efficacy of gene therapy using an adeno-associated virus serotype 1 carrying a human OTOF transgene (AAV1-hOTOF) in six children aged 1–18 years with DFNB9. The study found that five children treated with AAV1-hOTOF gene therapy experienced hearing recovery, with a 40–57 dB reduction in average auditory brainstem response (ABR) thresholds at 0.5–4.0 kHz.
One participant, who received a 9 × 10¹¹ vg dose of AAV1-hOTOF, showed ABR improvement from over 95 dB at baseline to 45 dB by week 26. Those who received a 1.5 × 10¹² vg dose had ABR improvements ranging from 38 to 55 dB. These findings…
