Device to Deliver Intra-Operative Therapeutic Hypothermia for Hearing Preservation in Cochlear Implantation

项目摘要 我们项目的目标是完成，验证，并准备监管批准的设备和探头， 向内耳提供局部的、受控的治疗性低温。器械安全性和有效性将 通过比较术前和术后，测试人工耳蜗植入手术中的残余听力保留 听力结果和术中电生理测量。广泛的临床前研究是 通过NIDCD R21和行业支持，允许开发低温输送协议， 使用适合于啮齿动物模型的装置和探针。我们建议在此重新设计设备和探测器， 在手术室进行临床植入，并准备进行监管批准。我们还将开展先行先试-- 通过实施局部治疗性低温来保护毛细胞， 人工耳蜗植入过程中的神经基质。这种方法带来了一种非药物治疗的残余 听力保护市场。此外，局限于内耳的低温避免了与耳内温度相关的挑战。 全身冷却或将药物递送到内耳。器械和探头不需要改变 手术方法或植入电极。具体目标是由我们的临床前研究， 表明低温可以长期保存人工耳蜗植入后的残余听力。确保 耳蜗中敏感毛细胞和神经结构的存活将导致改善的残余听力 保存，从长远来看可以改善语音感知结果。

Project Summary The goal of our project is to finalize, validate, and prepare for regulatory approvals a device and probe for delivering localized, controlled therapeutic hypothermia to the inner ear. The device safety and efficacy will be tested for residual hearing preservation in cochlear implant surgeries by comparing pre- and post-operative hearing outcomes and intra-operative electrophysiological measurements. Extensive preclinical research was enabled by a NIDCD R21 and industry support that allowed development of a protocol for hypothermia delivery using a device and probe suitable for a rodent model. We propose here to re-engineer the device and probe for clinical implantation in the operating room, and prepare it for regulatory approval. We will also carry out first-in- patient studies for the therapy by implementing localized, therapeutic hypothermia for protection of hair cells and neural substrate during cochlear implantation. This approach brings a non-pharmaceutical therapy for residual hearing preservation to the market. Furthermore, hypothermia localized to the inner ear avoids challenges with systemic cooling or with delivery of drugs to the inner ear. The device and probe do not require alteration of the surgical approach or the implant electrode. The specific aims are motivated by our preclinical studies that have shown that hypothermia can preserve residual hearing long-term post-cochlear implantation. Ensuring the survival of sensitive hair cells and neural structures in the cochlea will lead to improved residual hearing preservation, which in the long-term can improve speech perception outcomes.