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.

项目总结 声带麻痹(VFP)是嗓音、吞咽和呼吸道疾病的主要病因。常见原因 VFP包括喉外肿瘤、医源性损伤、神经功能障碍、气管插管等 创伤类型。特发性VFP(无明确病因)也很常见，约占VFP病例的三分之一。 这些患者的发声重建选择不是最理想的，而且没有微创的永久性 恢复声带活动度和功能的治疗选择。结果，许多患者留下了永久性的 失声和沟通障碍。本应用介绍了一种修复声带的新方法。 肌肉体积和功能对VFP治疗的影响。结果可能会带来新的、微创的治疗方案 这些患者的发声功能恢复。该应用程序的总体目标是使用基于成人干细胞的疗法 (改良的肌祖细胞)治疗VFP。当临床翻译时，这些细胞可以从 给病人，然后注射到病人瘫痪的声带作为永久治疗，可能 恢复运动和功能。我们目前正在进行这种模型在大型动物身上的临床前测试。 因此，这些具体目标的总体目标是发展细胞再神经治疗，在此之后 在动物模型中注射，证明：i)肌肉增大，随着时间的推移，体积损失最小 最小或没有异物反应，以及iii)失神经喉肌的健壮的、选择性的神经再支配。 拟议的研究结果应该会克服目前FDA批准的喉部的障碍 可注射物-这些障碍是随着时间的推移生物材料的完全吸收，导致异物反应 肉芽肿性反应/疤痕形成，缺乏治疗神经再支配的益处(除肿胀效应外)。 因为这些研究现在是在一个大型动物(猪)模型上进行的，它具有喉部的大小和功能 与人类非常相似的是，这些发现将具有很强的翻译性。这些实验的结果应该会导致 到里程碑式的临床创新，这将与语音恢复和其他外围设备的治疗相关 神经损伤。