Noninvasive System to Deliver Therapeutic Hypothermia for Protection Against Noise-Induced Hearing Loss

项目摘要 噪声性听力损失(NIHL)是全球性的公共健康风险，是一种不可逆转的损伤 对耳蜗内的敏感结构和神经元件造成损伤。疾病控制中心 和预防报告强调，美国24%的成年人和17%的青少年经历过听力 单耳或双耳因暴露在职业性或娱乐性的嘈杂声中而丧失。NIHL的发病率很高 对武装部队成员来说是一个严重的公共卫生问题，与生产力损失有关， 以及高昂的医疗费用。在全球范围内，职业性噪声暴露导致16%的失聪 损失(超过6亿人)；仅在美国，每个人的一生成本就很高。虽然有几个 药理药物在临床前试验和/或进入早期临床试验中显示出有希望的结果，网址为 目前还没有临床上可用的策略来减少或预防NIHL。初步结果和先前公布的结果 显示NIHL术后或术后向内耳提供的受控和局部治疗低温 机械性损伤保留了大量的残留听力，并保留了敏感的神经结构。这个 长期以来，人们一直在讨论治疗性低温对改善以下患者的神经预后的好处 创伤性脑损伤和心脏骤停。此第一阶段SBIR提案将用于设计、建造和测试 在危重期间向内耳非侵入性提供轻度治疗性低温的系统和方案 噪音创伤后的时间窗口。利用计算模型研究身体的传热学 这项研究的目的是将这种装置转化为临床实践。成功完成这些任务 第一阶段研究将使Restor-ear Devices LLC能够提交Q-Sub申请调查设备豁免 (IDE)给美国食品和药物管理局(FDA)和未来的第二阶段SBIR应用，以测试 人体NIHL的治疗性低温治疗。考虑到听力损失的流行率是 预计在接下来的几十年里，这些研究将显著增加，这将是朝着建立 治疗性低温作为一种保护听力的技术。我们的系统很可能会进一步发现 保护听觉和前庭功能免受耳毒性侮辱、创伤性脑损伤、冲击波的应用 暴露，内耳或中耳手术。

Project Summary Noise-induced hearing loss (NIHL) is global public health risk and is an impairment resulting from irreversible damage caused to the sensitive structures and neural elements in the cochlea. A Center for Disease Control and Prevention report highlights that 24% of adults and 17% of teenagers in the United States experience hearing loss in one or both ears from exposure to occupational or recreational loud sound. NIHL has a high prevalence among members of the armed forces and is a serious public health concern associated with loss of productivity, and high health care costs. Globally, occupational noise exposure is responsible for 16% of disabling hearing loss (over 600 million people); with significant lifetime costs per person in the US alone. While several pharmacological agents have shown promising results in preclinical trials and/or entered early clinical trials, at present there is no clinically available strategy to reduce or prevent NIHL. Preliminary and prior published results show that controlled and localized therapeutic hypothermia provided to the inner ear post-NIHL or post- mechanical trauma conserves significant residual hearing and preserves sensitive neural structures. The benefits of therapeutic hypothermia have long been discussed for improved neurological outcomes following traumatic brain injuries and cardiac arrest. This Phase I SBIR proposal will be used to design, build and test systems and protocols to deliver mild therapeutic hypothermia non-invasively to the inner ear during the critical time window following noise trauma. Using computational models of heat transfer and studies from cadaveric temporal bones, this study aims to translate such devices to clinical practice. Successful completion of these Phase I studies will enable Restor-Ear Devices LLC to submit a q-sub for an investigational device exemption (IDE) to the Food and Drug Administration and a future Phase II SBIR application to test efficacy and safety of therapeutic hypothermia against NIHL in human subjects. Considering that the prevalence of hearing loss is expected to increase significantly in the next few decades, these studies will be a first step toward establishing therapeutic hypothermia as a technique for preservation of hearing. It is likely that our systems will find further applications for protecting auditory and vestibular functions against ototoxic insults, traumatic brain injuries, blast exposures, and inner ear or middle ear surgeries.