Developing a Biomarker for Auditory Nerve Survival

项目摘要 听力损失是由于内耳受损，并可导致听神经退化 纤维和解剖结构中心的周围部位的病变。重要的是，越来越多的努力， 使用干细胞和其他基因疗法治愈听力损失。不幸的是，临床诊断测试不 具体确定造成听力损失的损伤的位置，或描述听力损失的生理学特征。 剩下的结构。因此，需要新的诊断测试，以确定损伤的部位， 治疗可以针对特定位置。这项研究的长期目标是开发这些 临床试验 听力损失患者的感知表现和满意度差异很大 助听器和人工耳蜗异质性的一个重要变量是从动物说明 研究和尸体研究，其中具有类似听力损失的受试者显示出各种解剖损伤。一 变异性的来源是听觉神经纤维群。听神经纤维可能会退化， 患者，而在另一些患者中则保持完整的补充。此外，最近在动物模型中发现， 即使是暂时性的听力损失，由于响亮的声音暴露，可以导致听神经退化， 听力临床测量的永久性变化。这种“隐性听力损失”沿着 听力损失患者听觉神经纤维的退化促使了这项研究的提出， 开发一种听觉神经存活的生物标志物。 听中耳肌反射可作为听神经存活的指标。的 解剖回路包括听神经，反射对拉伸或压缩 听神经测量MEM反射是听力学诊所的标准程序，用于识别 听神经肿瘤或压迫听神经的占位性肿瘤。其具体目的是 建议是确定MEM反射是否可以用作听神经变性的生物标志物。这是 通过记录动物模型中的MEM反射在应用药物之前和之后来完成，以 造成神经退化如果成功的话，这种生物标志物可用于识别神经系统疾病患者。 变性，以便靶向该部位进行组织移植。此外，确定神经的程度 存活率将有助于预测人工耳蜗植入和助听器的成功候选人，以及 为那些患有“隐性听力损失”的患者提供辅导。

PROJECT ABSTRACT Hearing loss results from damage to the inner ear, and can lead to degeneration of auditory nerve fibers and anatomic structures central to the peripheral sites of lesion. Importantly, there is growing effort to cure hearing loss using stem cells and other genetic treatments. Unfortunately, clinical diagnostic tests do not specifically identify the location of the insult that creates hearing loss, or describes the physiology of the remaining structures. Thus new diagnostic tests are needed that identify the site(s) of damage so that biologic treatments can be targeted to the specific location. The long term goal of this research is to develop these clinical tests. Patients with hearing loss vary considerably in their perceptual performance as well as their satisfaction with hearing aids and cochlear implants. An important variable in the heterogeneity is illustrated from animal studies and cadaver studies where subjects with similar hearing loss show a variety of anatomic damage. One source of variability is in the population of auditory nerve fibers. Auditory nerve fibers may degenerate in some patients whereas in others a full complement remains. Moreover, a recent finding in an animal model is that even temporary hearing loss, due to loud sound exposure, can cause auditory nerve degeneration without permanent changes in the clinical measures of hearing. This “hidden hearing loss” along with the degeneration of auditory nerve fibers in patients with hearing loss motivates the research in this proposal to develop a biomarker for auditory nerve survival. The acoustic middle ear muscle (MEM) reflex may serve as an index of auditory nerve survival. The anatomic circuit includes the auditory nerve, and the reflex is sensitive to stretching or compressing the auditory nerve. Measuring the MEM reflex is a standard procedure in Audiology clinics and is used to identify auditory nerve tumors or space-occupying tumors compressing the auditory nerve. The specific aim of this proposal is to determine if the MEM reflex can be used as a biomarker for auditory nerve degeneration. This is accomplished by recording the MEM reflex in an animal model before and after the application of a drug to create neural degeneration. If successful, this biomarker could be used to identify patients with neural degeneration in order to target this site for tissue transplantation. Moreover, determining the extent of neural survival will be useful for predicting successful candidates for cochlear implants and hearing aids, as well as counselling those patients with “hidden hearing loss”.