Gadenstaetter Anselm Joseph, Krumpoeck Paul Emmerich, Landegger Lukas David
Christian Doppler Laboratory for Inner Ear Research, Department of Otolaryngology, Head and Neck Surgery, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.
Department of Otolaryngology, Head and Neck Surgery, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.
Mol Diagn Ther. 2025 Mar;29(2):161-181. doi: 10.1007/s40291-024-00759-1. Epub 2024 Dec 3.
Hearing loss represents a highly prevalent and debilitating sensory disorder affecting roughly one in five people worldwide. In a majority of patients with congenital hearing loss, genetic mutations cause the disease. Up until recently, therapeutic options for individuals with hearing loss were limited to hearing aids and different types of auditory implants. However, after numerous years of intensive basic and translational research, gene therapy strategies are now being investigated in clinical trials. First results show significant hearing improvement in treated patients, highlighting gene therapy's role as a promising treatment for certain forms of genetic hearing loss. In this article, we provide an overview of genetic hearing loss and inner ear gene therapy research including relevant strategies that have been established in animal models and will likely be investigated in human patients soon. Furthermore, we summarize and contextualize the novel findings of recently completed and ongoing clinical trials, and discuss future hurdles needed to be overcome to allow for a broad and safe clinical application of inner ear gene therapy.
听力损失是一种非常普遍且使人衰弱的感觉障碍,全球约五分之一的人受其影响。在大多数先天性听力损失患者中,基因突变导致了这种疾病。直到最近,听力损失患者的治疗选择还仅限于助听器和不同类型的听觉植入物。然而,经过多年深入的基础研究和转化研究,基因治疗策略目前正在临床试验中进行研究。初步结果显示,接受治疗的患者听力有显著改善,这突出了基因治疗在某些形式的遗传性听力损失治疗中作为一种有前景的治疗方法的作用。在本文中,我们概述了遗传性听力损失和内耳基因治疗研究,包括在动物模型中已确立且可能很快将在人类患者中进行研究的相关策略。此外,我们总结并梳理了最近完成和正在进行的临床试验的新发现,并讨论了为实现内耳基因治疗广泛且安全的临床应用所需克服的未来障碍。