Hickox Ann E, Larsen Erik, Heinz Michael G, Shinobu Leslie, Whitton Jonathon P
Decibel Therapeutics, 215 First St, Cambridge, MA, 02142, USA.
Speech, Language, and Hearing Sciences and Biomedical Engineering, Purdue University, 715 Clinic Drive, West Lafayette, IN, 47907, USA.
Hear Res. 2017 Jun;349:164-171. doi: 10.1016/j.heares.2016.12.010. Epub 2017 Jan 7.
Understanding the biology of the previously underappreciated sensitivity of cochlear synapses to noise insult, and its clinical consequences, is becoming a mission for a growing number of auditory researchers. In addition, several research groups have become interested in developing therapeutic approaches that can reverse synaptopathy and restore hearing function. One of the major challenges to realizing the potential of synaptopathy rodent models is that current clinical audiometric approaches cannot yet reveal the presence of this subtle cochlear pathology in humans. This has catalyzed efforts, both from basic and clinical perspectives, to investigate novel means for diagnosing synaptopathy and to determine the main functional consequences for auditory perception and hearing abilities. Such means, and a strong concordance between findings in pre-clinical animal models and clinical studies in humans, are important for developing and realizing therapeutics. This paper frames the key outstanding translational questions that need to be addressed to realize this ambitious goal.
了解耳蜗突触对噪声损伤的先前未被充分认识的敏感性及其临床后果的生物学机制,正成为越来越多听觉研究人员的一项任务。此外,几个研究小组已对开发能够逆转突触病变并恢复听力功能的治疗方法产生兴趣。实现突触病变啮齿动物模型潜力的主要挑战之一是,目前的临床听力测试方法尚无法揭示人类中这种微妙的耳蜗病理状况的存在。这促使从基础和临床角度进行努力,以研究诊断突触病变的新方法,并确定对听觉感知和听力能力的主要功能影响。这些方法以及临床前动物模型的研究结果与人类临床研究之间的高度一致性,对于开发和实现治疗方法很重要。本文阐述了为实现这一宏伟目标需要解决的关键突出转化问题。