Frequency Therapeutics, Lexington, Massachusetts.
Department of Otolaryngology, Central Institute for the Deaf, Fay and Carl Simons Center for Hearing and Deafness, Washington University School of Medicine, Saint Louis, Missouri.
J Am Acad Audiol. 2021 Nov;32(10):661-669. doi: 10.1055/s-0042-1750281. Epub 2022 May 24.
Sensorineural hearing loss (SNHL) is typically a permanent and often progressive condition that is commonly attributed to sensory cell loss. All vertebrates except mammals can regenerate lost sensory cells. Thus, SNHL is currently only treated with hearing aids or cochlear implants. There has been extensive research to understand how regeneration occurs in nonmammals, how hair cells form during development, and what limits regeneration in maturing mammals. These studies motivated efforts to identify therapeutic interventions to regenerate hair cells as a treatment for hearing loss, with a focus on targeting supporting cells to form new sensory hair cells. The approaches include gene therapy and small molecule delivery to the inner ear. At the time of this publication, early-stage clinical trials have been conducted to test targets that have shown evidence of regenerating sensory hair cells in preclinical models. As these potential treatments move closer to a clinical reality, it will be important to understand which therapeutic option is most appropriate for a given population. It is also important to consider which audiological tests should be administered to identify hearing improvement while considering the pharmacokinetics and mechanism of a given approach. Some impacts on audiological practice could include implementing less common audiological measures as standard procedure. As devices are not capable of repairing the damaged underlying biology, hair-cell regeneration treatments could allow patients to benefit more from their devices, move from a cochlear implant candidate to a hearing aid candidate, or move a subject to not needing an assistive device. Here, we describe the background, current state, and future implications of hair-cell regeneration research.
感音神经性听力损失（SNHL）通常是一种永久性的，且往往是渐进性的疾病，通常归因于感觉细胞的丧失。除哺乳动物以外的所有脊椎动物都可以再生失去的感觉细胞。因此，目前 SNHL 仅通过助听器或人工耳蜗植入来治疗。为了理解非哺乳动物中再生是如何发生的、毛细胞在发育过程中是如何形成的以及是什么限制了成熟哺乳动物的再生，已经进行了广泛的研究。这些研究促使人们努力寻找治疗干预措施，以再生毛细胞作为治疗听力损失的方法，重点是针对支持细胞以形成新的感觉毛细胞。这些方法包括基因治疗和将小分子递送到内耳。在本出版物发表之时，已经进行了早期临床试验，以测试在临床前模型中显示出再生感觉毛细胞证据的靶点。随着这些潜在治疗方法更接近临床现实，了解哪种治疗选择最适合特定人群将非常重要。考虑到特定方法的药代动力学和机制，考虑哪些听力学测试应该进行以确定听力改善也很重要。一些对听力学实践的影响可能包括将不常见的听力学措施作为标准程序实施。由于设备无法修复受损的基础生物学，因此毛细胞再生治疗可以使患者从设备中受益更多，可以使患者从人工耳蜗植入候选者转变为助听器候选者，或者使患者不再需要辅助设备。在这里，我们描述了毛细胞再生研究的背景、现状和未来意义。
