Cellular Reinnervation Therapy for Vocal Fold Paralysis

声带麻痹的细胞神经再生疗法

• 批准号: 10627993
• 负责人: Stacey L. Halum
• 金额: $ 62.24万
• 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/10627993
• 关键词: Animal Model; Animals; Aphonia; Atrophic; Attenuated; Autologous; Biocompatible Materials; Biomedical Engineering; Biopsy; Cell Therapy; Cells; Cicatrix; Clinic; Clinical; Collaborations; Collagen; Communication impairment; Data; Deglutition; Denervation; Diameter; Disease; Dysphonia; Electromyography; Etiology; FDA approved; Family suidae; Foreign-Body Reaction; Goals; Granulomatous; Human; In Situ; Individual; Injectable; Injections; Injury; Intratracheal Intubation; Laboratories; Laryngeal Nerves; Laryngeal muscle structure; Laryngeal neoplasm; Laryngoscopy; Larynx; Left; Legal patent; Liquid substance; Medial; Methods; Modeling; Motion; Motor Endplate; Muscle; Muscle Cells; Muscle satellite cell; Nerve; Paralysed; Patients; Peripheral nerve injury; Persons; 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; adduct; adult stem cell; bench to bedside; biomaterial compatibility; clinical translation; collagen scaffold; cost; delivery vehicle; 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; 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.

项目概要 声带麻痹 (VFP) 是声音、吞咽和气道疾病的主要病因。常见原因 VFP包括喉外肿瘤、医源性损伤、神经系统疾病、气管插管和其他 创伤类型。特发性 VFP（无明确病因）也很常见，约占 VFP 病例的 1/3。 这些患者的声音恢复选择不是最理想的，并且没有微创永久性治疗方法 恢复声带活动性和功能的治疗方案。结果，许多患者留下了永久性的 声音丧失和沟通障碍。该应用程序介绍了一种恢复声带的新方法 用于治疗 VFP 的肌肉体积和功能。结果可能会带来新颖的、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体干细胞的疗法 （一种改良的肌肉祖细胞）治疗 VFP。当临床转化时，这些细胞可以来源于 给患者，然后注射到该患者瘫痪的声带作为永久性治疗，有可能 恢复运动和功能。我们目前正在大型动物中对这种模型进行临床前测试。 因此，这些具体目标的总体目标是开发细胞神经支配疗法， 在动物模型中注射，证明：i) 肌肉增强，随着时间的推移，体积损失最小 ii) 异物反应极小甚至无异物反应；iii) 去神经支配的喉肌的强健、选择性神经再支配。 拟议研究的结果应该克服当前 FDA 批准的喉部药物的障碍 注射剂——这些障碍是生物材料随着时间的推移完全吸收，导致异物反应 肉芽肿反应/疤痕，并且缺乏神经支配治疗益处（除了膨胀效应）。 因为这些研究现在正在大型动物（猪）模型中进行，具有喉部大小和功能 与人类非常相似，研究结果将具有高度转化性。这些实验的结果应该导致 具有里程碑意义的临床创新，这些创新将与声音恢复和其他外周疾病的治疗相关 神经损伤。

项目成果

Impact of Needle Selection on Survival of Muscle-Derived Cells When Used for Laryngeal Injections.

当用于喉部注射时，针头选择对肌肉衍生细胞存活的影响。

• DOI: pii: 377
• 发表时间: 2023
• 期刊: Journal of cell science & therapy
• 作者: Awonusi O;Harbin ZJ;Brookes S;Zhang L;Kaefer S;Morrison RA;Newman S;Voytik-Harbin S;Halum S
• 通讯作者: Halum S