Core Viewpoint - The article discusses the significant advancements in gene therapy for hereditary hearing loss, particularly focusing on the OTOF gene and its implications for treatment effectiveness and safety [1][2][3]. Group 1: Gene Therapy Developments - Approximately 430 million people globally suffer from disabling hearing loss, with 26 million cases being congenital, 60% of which are linked to genetic susceptibility [1]. - Over 200 genes have been identified in relation to hereditary hearing loss, yet no approved drugs or therapies exist for treating genetic hearing loss [1]. - AAV-mediated gene replacement strategies and CRISPR-Cas gene editing technologies are the primary research directions in the field of gene therapy for hearing loss [1]. Group 2: Clinical Research Findings - In January 2024, a clinical study published in The Lancet demonstrated the safety and efficacy of AAV-mediated gene therapy in children with severe hearing impairment due to OTOF gene mutations [2]. - A subsequent study published in Nature Medicine in June 2024 confirmed the positive outcomes of bilateral gene therapy, reinforcing the initial findings [2]. - The physiological mechanisms involved in hearing recovery for DFNB9 patients include the restoration of inner ear hair cell synaptic vesicle release and the reorganization of central auditory pathways [2]. Group 3: Audiological Assessments - A study published in May 2025 analyzed audiological characteristics post-gene therapy in DFNB9 patients, providing critical data for evaluating treatment effectiveness [3]. - The assessment involved 10 patients, with evaluations using auditory brainstem response (ABR), auditory steady-state response (ASSR), pure tone audiometry (PTA), and distortion product otoacoustic emissions (DPOAE) [5]. - Results indicated significant improvements in hearing, with ABR showing clear V waves in all patients by 13 weeks post-treatment, and a notable reduction in V wave latency [6]. Group 4: Implications for Future Research - The study highlighted the correlation between PTA, ABR, and ASSR thresholds, validating their effectiveness as clinical assessment tools for hearing recovery [7]. - The findings suggest that while gene therapy restores inner ear hair cell function, it does not significantly impact outer hair cell function as measured by DPOAE [7]. - The combination of subjective (PTA) and objective (ABR, ASSR) assessment tools is recommended for comprehensive auditory evaluation, with further clinical validation needed to optimize treatment strategies and assess long-term effects [9].