Core Insights - A research team led by Fudan University and Seoul National University has developed a potential precision treatment strategy for hereditary hearing loss, recently published in the journal Nature Communications [1][2] - Hearing impairment is one of the most common sensory disorders, affecting approximately 430 million people globally, which is about 5% of the world's population [1] - The study identified MPZL2 gene mutations as a common cause of hereditary mild to moderate sensorineural hearing loss (SNHL) in East Asian populations, with specific mutations showing a founder effect [1] Group 1 - The research involved a systematic etiological analysis of 1,437 unrelated hereditary hearing loss families, identifying pathogenic genes in 155 patients, with 24 cases linked to MPZL2 mutations, accounting for 15.5% [1] - Among the identified cases, 23 patients carried at least one c.220C>T allele mutation, representing a high prevalence of 95.8%, suggesting it may be a founder mutation in East Asia [1] Group 2 - The team created a humanized mouse model that replicated the auditory phenotype of human patients with MPZL2 gene mutations [2] - A novel adenine base editor system with enhanced flexibility was developed, successfully correcting the abnormal expression of the MPZL2 gene, leading to significant hearing recovery in the mouse model for at least 20 weeks without noticeable off-target effects [2] - This research not only offers a potential treatment strategy for hereditary hearing loss but also expands the application of single-base editing technology in genetic diseases [2]

Core Viewpoint - The collaboration between Fudan University and Seoul National University Hospital has led to significant advancements in gene therapy for hereditary hearing loss, specifically targeting the MPZL2 gene mutation prevalent in East Asian populations, offering potential precision treatment strategies for genetic hearing loss [3][8][19]. Group 1: Research Findings - The study published in Nature Communications demonstrates that a flexible adenine base editor (ABE) can rescue hearing loss in a humanized MPZL2 mouse model with an East Asian founder mutation [3][8]. - Approximately 4.3 billion people globally suffer from disabling hearing loss, with 26 million being congenital cases, highlighting the urgent need for effective treatments [6]. - The MPZL2 gene mutation is identified as a significant cause of autosomal recessive non-syndromic hearing loss, with specific mutations like c.220C>T being common in East Asian populations [7][8]. Group 2: Gene Therapy Innovations - The research team developed a PAM-flexible ABE variant that minimizes off-target effects and successfully restored hearing in mutant mice for at least 20 weeks [9][11]. - The dual-AAV delivery system was utilized to correct abnormal gene expression and restore the integrity of the inner ear structure in the mouse model [11][21]. - The team has previously achieved significant milestones in gene therapy for congenital hearing loss, including the first-in-human clinical trial for OTOF gene therapy, which has shown promising results in restoring hearing and speech [20][24]. Group 3: Future Implications - The advancements in gene therapy for hearing loss could pave the way for treatments of other genetic disorders, enhancing confidence in the application of ABE technology [11][29]. - The research findings have been recognized in top medical journals, indicating a paradigm shift in the treatment of hearing loss and the potential for broader applications in genetic diseases [24][29].