Cellular Reinnervation Therapy for Vocal Fold Paralysis

声带麻痹的细胞神经再生疗法

• 批准号: 10276585
• 负责人: Stacey L. Halum
• 金额: $ 65.7万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-04 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10276585
• 关键词: Animal Model; Animals; Aphonia; Atrophic; Attenuated; Autologous; Biocompatible Materials; Biomedical Engineering; Biopsy; Caliber; Cell Therapy; Cells; Cicatrix; Clinic; Clinical; Collaborations; Collagen; Communication impairment; Data; Deglutition; Denervation; Disease; Dysphonia; Electromyography; Etiology; FDA approved; Foreign-Body Reaction; Goals; Granulomatous; Human; In Situ; Individual; Injectable; Injections; Injury; Intratracheal Intubation; Laboratories; Laryngeal Nerves; Laryngeal muscle structure; Laryngeal neoplasm; Laryngoscopy; Larynx; Lead; Left; Legal patent; Liquid substance; Medial; Methods; Modeling; Motion; Motor Endplate; Muscle; Muscle Cells; Muscle satellite cell; Nerve; Paralysed; Patients; Peripheral nerve injury; Physicians; Positioning Attribute; Preclinical Testing; Procedures; Reaction; Recovery of Function; Recurrent Laryngeal Nerve; Safety; Saline; Savings; Scientist; Symptoms; Therapeutic; Thyroarytenoid Muscle; Time; Translating; Trauma; United States; Voice; Voice Quality; adult stem cell; base; bench to bedside; biomaterial compatibility; clinical translation; cost; experimental study; functional restoration; iatrogenic injury; innovation; minimally invasive; muscle reinnervation; nerve damage; nerve injury; nerve supply; nerve transection; nervous system disorder; neurotrophic factor; novel; novel strategies; porcine model; pressure; reinnervation; repaired; restoration; scaffold; stem cell therapy; symptomatic improvement; therapy outcome; vocal cord

PROJECT SUMMARY Vocal fold paralysis (VFP) is a major etiology of voice, swallowing, and airway disorders. Common causes of VFP include extra-laryngeal neoplasm, iatrogenic injury, neurologic disorder, endotracheal intubation, and other types of trauma. Idiopathic VFP (with no clear cause) is also common, constituting roughly 1/3 of VFP cases. Voice restoration options for these patients are suboptimal, and there are no minimally invasive permanent treatment options to restore vocal fold mobility and function. As a result, many patients are left with permanent voice loss and communication impairment. This application introduces a novel approach for restoring vocal fold muscle volume and function for the treatment of VFP. Results may lead to novel, minimally invasive options for voice restoration in these patients. The overall goal of the application is to use an adult stem cell based therapy (a modified muscle progenitor cell) to treat VFP. When clinically translated these cells can be derived from a given patient, and then injected into that patient's paralyzed vocal fold as a permanent treatment, potentially restoring both motion and function. We are currently doing preclinical testing of such a model in a large animal. Thus, these specific aims have the overall goal of developing cellular reinnervation therapy, which, after injection in an animal model, demonstrates: i) muscle augmentation with minimal loss of volume over time ii) minimal to no foreign body reaction and iii) robust, selective reinnervation of the denervated laryngeal muscle. Findings from the proposed studies should overcome the hurdles of current FDA approved laryngeal injectables—those hurdles being complete resorption of biomaterial over time, foreign body reactions resulting in granulomatous reaction/scarring, and lack of therapeutic reinnervation benefit (beyond a bulking effect). Because these studies are being done now in a large animal (porcine) model, with laryngeal size and function very similar to that of humans, findings will be highly translational. Results from these experiments should lead to landmark clinical innovations that will be relevant to both voice restoration and treatment of other peripheral nerve injuries.

项目摘要 声带麻痹（VFP）是嗓音、吞咽和气道疾病的主要病因。的常见原因 VFP包括喉外肿瘤、医源性损伤、神经系统疾病、气管插管和其他 创伤的类型。特发性VFP（没有明确的原因）也很常见，约占VFP病例的1/3。 这些患者的声音恢复选择是次优的，并且没有微创永久性的。 治疗方案，以恢复声带的流动性和功能。因此，许多患者留下了永久性的 语音损失和沟通障碍。这个应用程序介绍了一种新的方法来恢复声带 肌肉体积和功能的治疗VFP。结果可能会导致新的，微创的选择， 这些患者的声音恢复。该应用程序的总体目标是使用基于成人干细胞的治疗 （一种修饰的肌肉祖细胞）来治疗VFP。当临床翻译时，这些细胞可以来源于 给病人，然后注射到病人瘫痪的声带作为永久性治疗， 恢复运动和功能。我们目前正在大型动物中进行这种模型的临床前测试。 因此，这些具体目标具有开发细胞神经再支配疗法的总体目标， 在动物模型中注射，证明：i）肌肉增强，随着时间的推移具有最小的体积损失ii） 最小至无异物反应和iii）去神经支配的喉肌的稳健的选择性神经再支配。 从拟议的研究结果应该克服目前FDA批准的喉的障碍 注射剂-这些障碍是随着时间的推移生物材料完全吸收，导致异物反应， 肉芽肿反应/瘢痕形成，以及缺乏治疗性神经再支配益处（超出膨胀效应）。 因为这些研究是在一个大型动物（猪）模型中进行的，喉的大小和功能 与人类非常相似，研究结果将具有高度的转化性。这些实验的结果应该会导致 具有里程碑意义的临床创新，这将是相关的声音恢复和治疗其他周边 神经损伤