Vestibular Implantation to Treat Adult-Onset Bilateral Vestibular Hypofunction

项目摘要 双侧前庭感觉丧失是无效的，受影响的人患有慢性平衡失调， 跌倒的风险增加，在日常生活中典型的头部运动时无法保持稳定的视力。而当 大多数有轻微损失的人通过利用其他感官的康复策略进行补偿，那些 对于严重的损失，那些不能补偿的人没有好的治疗选择。当前庭神经 在解剖学上是完好无损的，就像在大多数情况下一样，编码头部旋转的电刺激可以驱动神经 活动和部分恢复前庭感觉，就像人工耳蜗部分恢复听觉一样 轰动一时。在一项正在进行的人类首例双侧前庭致残成人早期可行性研究中 耳毒性毛细胞损伤后功能减退，我们发现前庭植入和运动调节 以植入耳三个半规管为靶点的假体刺激是一种可行、安全、有效的方法 治疗耳毒性丧失，以可靠地诱发定向排列的前庭-眼反射为证据 在连续使用3年期间，姿势和步态性能的客观测量有所改善，以及 患者报告的眩晕、残疾和前庭相关残疾的改善。基于这些力量的力量 结果，美国食品和药物管理局(FDA)邀请了人道主义设备的请求 耳毒性丧失的治疗豁免；然而，FDA建议需要更多的数据来 支持将这种治疗扩大到特发性损失的个人，他们构成了最大的 双侧前庭功能减退病例所占比例。依靠一支成熟的设计，完整的研究团队， 以及在耳毒性丧失受试者的早期可行性研究中产生高度影响的方案， 拟议的研究计划将把这种方法扩展到因特发性成人双侧起病而致残的成年人 前庭功能减退。这项研究的结果极有可能产生广泛、持续的影响， 通过支持早期监管批准(如果前庭植入治疗特发性耳聋的结果 与已经获得的耳毒性丧失结果一样有利)或通过提供必要的基础 数据支持随后的前庭植入治疗特发性耳聋的大规模关键试验的设计。

Project Summary Bilateral loss of vestibular sensation is disabling, with affected individuals suffering chronic disequilibrium, increased risk of falls, and inability to maintain stable vision during head movements typical of daily life. While most individuals with milder loss compensate through rehabilitative strategies enlisting other senses, those with severe loss who fail to compensate have no good therapeutic options. When the vestibular nerves are anatomically intact, as is true in most such cases, electrical stimuli encoding head rotation can drive nerve activity and partially restore vestibular sensation, much as a cochlear implant partially restores auditory sensation. In an on-going first-in-human early feasibility study of six adults disabled by bilateral vestibular hypofunction after ototoxic hair cell injury, we found that vestibular implantation and motion-modulated prosthetic stimulation targeting the implanted ear's three semicircular canals is a feasible, safe and effective treatment for ototoxic loss, as evidenced by directionally-aligned vestibulo-ocular reflexes reliably elicited during >3 years of continuous use, improvements in objective measures of posture and gait performance, and improvement of patient-reported dizziness handicap and vestibular-related disability. On the strength of those results, the United States Food & Drug Administration (FDA) has invited a request for humanitarian device exemption for treatment of ototoxic loss; however, FDA advised that additional data would be required to support expanding availability of this treatment to individuals with idiopathic loss, who make up the largest proportion of bilateral vestibular hypofunction cases. Drawing on a well-established design, intact study team, and protocol that yielded highly impactful results in the early feasibility study of subjects with ototoxic loss, the proposed research program will extend this approach to adults disabled by idiopathic adult-onset bilateral vestibular hypofunction. Results of this research are highly likely to yield broad, sustained impact, either through support of early regulatory approval (if results of vestibular implantation for treatment of idiopathic loss are as favorable as the results already obtained for ototoxic loss) or by providing the necessary foundational data to support design of a subsequent, large-scale pivotal trial of vestibular implantation for idiopathic loss.