Efficacy of Targeted Therapy for Hearing Loss-Causing Gene Variants Confirmed

On December 23, Professor Jinse Jeong from the Department of Otorhinolaryngology at Severance Hospital, Professor Heonyoung Ji from the Department of Pharmacology at Yonsei University College of Medicine, and the research team led by Lecturer Seunghyun Jang announced that they have confirmed the effectiveness of gene therapy for MPZL2 variants, the most common cause of mild-to-moderate hearing loss among Koreans.

The results of this study were published in the international academic journal Molecular Therapy (Impact Factor 12).

Professor Jinse Jeong, Department of Otorhinolaryngology, Severance Hospital; Professor Heonyeong Ji, Department of Pharmacology, Yonsei University College of Medicine; Research team led by Lecturer Seunghyun Jang, Yonsei Medical Center

One of the main causes of hearing loss is genetic mutation. In particular, MPZL2 gene variants are a common cause of mild-to-moderate hereditary hearing loss among East Asians, where sounds must be at least 26 to 55 dB to be perceived. Currently, there are no biological therapeutics available to restore or prevent the progression of hereditary hearing loss caused by MPZL2 variants.

The research team analyzed genomic data from the Yonsei University Hearing Loss cohort, which they had previously established, and confirmed that MPZL2 gene variants are a common cause of mild-to-moderate hearing loss among Koreans.

Furthermore, they identified a founder variant, meaning a mutation that originated from a small number of ancestors and has spread at a relatively high frequency within the population over generations. The most common variant found in Koreans was a founder variant in the MPZL2 gene, where a premature stop signal occurs at the 74th amino acid position, leading to truncated protein synthesis.

The team created a mouse model carrying the founder variant and administered gene therapy by delivering the MPZL2 gene into the inner ear using a virus-based vector. The mouse model showed up to a 40 dB improvement in hearing at certain frequencies, and the effect lasted for more than six months.

Professor Jinse Jeong stated, "Until now, there has been no safe and effective treatment for mild-to-moderate hearing loss, but we have proposed a gene therapy that is effective for all types of MPZL2 variants that frequently cause this condition. In the future, we aim to enhance treatment safety for clinical application by refining targeted cell delivery and regulating gene expression levels."