Saeed Ahmad, Younis Osama, Al-Awamleh Nada, Qubbaj Fares, Al-Sharif Zeid, Sulaiman Samia, Al-Taher Mohammad, Khreesha Lubna
School of Medicine, University of Jordan, Amman, Jordan.
Department of Special Surgeries, School of Medicine, University of Jordan, Amman, Jordan.
Hum Gene Ther. 2025 Jul;36(13-14):989-1003. doi: 10.1089/hum.2025.013. Epub 2025 Jun 12.
Sensorineural hearing loss (SNHL) is the most common sensory deficit globally. Acquired SNHL results from ototoxic damage to cochlear hair cells (HCs) and is typically irreversible due to their limited regenerative capacity. While no cure currently exists, targeting the underlying pathology offers potential. Preclinical studies have investigated transcription factors like ATOH1, which can induce non-sensory cells to transdifferentiate into HCs. Gene therapy using viral vectors to deliver is emerging as a promising regenerative approach. PubMed, Web of Science, and Embase were systematically searched. The review was conducted following the Systematic Review Center for Laboratory Animal Experimentation guidelines. Random-effects meta-analysis was conducted using R's "meta" and "metafor" packages. To corroborate our findings, differential gene expression (DEG) analysis was performed on the GEO dataset GSE127683 using DESeq2. K-means clustering and gene set enrichment analysis (GSEA) were conducted using iDEP 2.0 and Enrichr, respectively. Four studies including 52 rodents were included. gene therapy significantly reduced Auditory Brainstem Response thresholds ( dB SPL, CI: [-40.19; -2.54], = 0.027), indicating improved hearing. DEG analysis showed upregulation of genes crucial for hair cell differentiation and functioning, including GFI1, PTPRQ, OTOF, USH2A, and POU4F3. GSEA highlighted key upregulated pathways related to inner ear development, auditory receptor cell differentiation and sensory perception of sound. gene therapy shows promise for treating acquired SNHL. However, further clinical trials are essential to confirm these preclinical findings and advance towards a potential cure.
感音神经性听力损失（SNHL）是全球最常见的感觉缺陷。获得性SNHL是由耳蜗毛细胞（HCs）的耳毒性损伤引起的，由于其有限的再生能力，通常是不可逆的。虽然目前尚无治愈方法，但针对潜在病理机制具有一定潜力。临床前研究已经对诸如ATOH1等转录因子进行了研究，这些转录因子可以诱导非感觉细胞转分化为毛细胞。使用病毒载体进行基因治疗作为一种有前景的再生方法正在兴起。我们系统检索了PubMed、科学网和Embase。本综述按照实验动物实验系统评价中心的指南进行。使用R语言的“meta”和“metafor”包进行随机效应荟萃分析。为了证实我们的发现，使用DESeq2对GEO数据集GSE127683进行差异基因表达（DEG）分析。分别使用iDEP 2.0和Enrichr进行K均值聚类和基因集富集分析（GSEA）。纳入了四项研究，共52只啮齿动物。基因治疗显著降低了听觉脑干反应阈值（dB SPL，置信区间：[-40.19；-2.54]，P = 0.027），表明听力有所改善。DEG分析显示，对毛细胞分化和功能至关重要的基因上调，包括GFI1、PTPRQ、OTOF、USH2A和POU4F3。GSEA突出了与内耳发育、听觉受体细胞分化和声音感觉感知相关的关键上调通路。基因治疗显示出治疗获得性SNHL的潜力。然而，进一步的临床试验对于证实这些临床前发现并朝着潜在的治愈方法迈进至关重要。
