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

项目摘要 我们项目的目标是最终确定、验证设备和探测器的监管审批并为其做准备 将局部的、可控的治疗性低温输送到内耳。该装置的安全性和有效性将是 人工耳蜗植入术前后听力保留的对比研究 听力结果和术中电生理测量。广泛的临床前研究是 由NIDCD R21和允许开发低温传输协议的行业支持实现 使用适合啮齿动物模型的装置和探头。我们建议在这里重新设计该设备，并探索 在手术室进行临床植入，并准备等待监管部门的批准。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和 人工耳蜗术中的神经基质。这种方法为残留物带来了一种非药物疗法 将听力保全推向市场。此外，局限于内耳的低温可避免挑战 全身降温或向内耳输送药物。该设备和探头不需要更改 手术入路或植入电极。具体目标是由我们的临床前研究推动的，这些研究已经 结果表明，低温可长期保存人工耳蜗术后的残余听力。确保 耳蜗内敏感毛细胞和神经结构的存活将改善残余听力 保存，从长远来看，这可以改善言语感知结果。

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.