Cellular Reinnervation Therapy for Vocal Fold Paralysis

声带麻痹的细胞神经再生疗法

基本信息

批准号：
10461958
负责人：
Stacey L. Halum
金额：
$ 63.72万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
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/10461958
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 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 adult stem cell base 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 porcine model pressure reinnervation repaired restoration scaffold stem cell therapy symptomatic improvement therapy outcome vocal cord

项目摘要

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.

项目摘要声带瘫痪（VFP）是声音，吞咽和气道疾病的主要病因。常见原因 VFP包括诊断外肿瘤，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（没有明确原因）也很常见，大约构成了VFP病例的1/3。这些患者的语音恢复选择是次优的，并且没有最小的侵入性永久性恢复人声折叠机动性和功能的治疗选择。结果，许多患者被永久保留语音丧失和沟通障碍。该应用程序引入了一种恢复人声折叠的新方法 VFP治疗的肌肉体积和功能。结果可能会导致新颖的，微创的选择这些患者的语音恢复。应用的总体目标是使用基于成人干细胞的疗法（改良的肌肉祖细胞）治疗VFP。当临床翻译时，这些细胞可以从A 给予患者，然后注入该患者的瘫痪声折，作为永久治疗，可能还原运动和功能。我们目前正在大型动物中对这种模型进行临床前测试。这是这些特定目的的总体目标是开发细胞加剧疗法，该疗法之后在动物模型中注射，证明：i）肌肉的增强，在II期间的体积损失最少）最小化，也没有外国反应，iii）坚固的，可重新连接的喉部肌肉。拟议研究的发现应克服当前FDA批准的喉的障碍注射剂 - 随着时间的流逝，这些障碍是完全解决生物材料的完全解决在肉芽肿反应/疤痕中，缺乏治疗性再交受益（超出散装效果）。因为这些研究现在正在大型动物（猪）模型中进行，喉大小和功能与人类非常相似，发现将被高度翻译。这些实验的结果应引导具有里程碑意义的临床创新，这将与其他周围的语音恢复和处理有关神经损伤。