ATOH-1 Gene Therapy in Acquired Sensorineural Hearing Loss: A Meta-Analysis and Bioinformatic Analysis of Preclinical Studies

Authors:
Publisher website
Google Scholar
Abstract
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 ATOH1 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. ATOH1 gene therapy significantly reduced Auditory Brainstem Response thresholds ( MD = −21.37 dB SPL, CI: [−40.19; −2.54], p = 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. ATOH1 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.

This publication has 31 references indexed in Scilit: