Project 3: Treatment of mucostasis and airways obstruction in CF with a novel mucolytic

项目 3：用新型粘液溶解剂治疗 CF 中的粘膜淤积和气道阻塞

基本信息

批准号：
9356820
负责人：
SCOTT H DONALDSON
金额：
$ 27.21万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-07 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9356820
关键词：
Abnormal ion transport Adverse event Affect Agar Gel Electrophoresis Asthma Biological Assay Biological Markers Breathing Bronchiectasis Cessation of life Chelating Agents Chronic Chronic Bronchitis Chronic Obstructive Airway Disease Clinical Clinical Trials Collection Cross-Over Studies Cysteine Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator DNA Data Dehydration Detergents Development Disease Disease model Dose Drug Kinetics Exhalation Frequencies Gel Goals Health Healthcare Hydration status Impairment In Vitro Ion Transport Laboratories Lead Lung Lung diseases Magnetic Resonance Imaging Measurement Measures Modality Molecular Monitor Morbidity - disease rate Mucins Mucociliary Clearance Mucolytics Mucous body substance Obstruction Obstructive Lung Diseases Outcome Measure Pathogenesis Pathologic Patients Pharmaceutical Preparations Phase Placebo Control Process Property Pulmonary Cystic Fibrosis Pulmonary Function Test/Forced Expiratory Volume 1 Radionuclide Imaging Randomized Reducing Agents Reporting Research Respiratory physiology Safety Saline Science Severities Sputum Sulfhydryl Compounds Symptoms Syndrome Testing Therapeutic Therapeutic Agents Western Blotting airway obstruction base cystic fibrosis airway cystic fibrosis patients disability disulfide bond extracellular healthy volunteer human disease improved indexing mortality novel novel therapeutics premature pulmonary function recombinant human DNase safety testing surfactant targeted agent therapy development

项目摘要

PROJECT SUMMARY Mucus obstruction of airways is a significant pathologic feature of CF lung disease. Available therapies are only partially effective at relieving this obstruction, and additional treatments are needed. Gel-forming mucin molecules are a major constituent of CF mucus and to a large degree determines its bio-rheological properties. The development of inhaled agents that target mucin molecules and improve the transportability of airway mucus is a rational and attractive therapeutic goal. In this Project, we propose to first test the safety of a novel inhaled mucolytic in CF subjects in a single ascending dose study. We will then evaluate the ability of this agent to improve mucus clearance and reduce airways obstruction during two weeks of use, in a placebo controlled cross-over study in CF. Relevant, novel outcome measures will be utilized to evaluate drug effects on mucus clearance (gamma scintigraphy) and airways obstruction (19F-MRI with 1H-MRI/UTE), in addition to traditional clinical trial endpoints. The combination of these functional and structural modalities should greatly enhance our understanding of drug effects on this heterogeneous lung disease.

项目概要气道粘液阻塞是 CF 肺病的一个重要病理特征。可用的疗法有对于缓解这种阻塞仅部分有效，并且需要额外的治疗。凝胶形成粘蛋白分子是 CF 粘液的主要成分，在很大程度上决定了其生物流变特性。开发针对粘蛋白分子并改善气道输送性的吸入剂粘液是一个合理且有吸引力的治疗目标。在这个项目中，我们建议首先测试小说的安全性在单次剂量递增研究中，CF 受试者吸入粘液溶解剂。然后我们将评估这个能力使用两周内改善粘液清除并减少气道阻塞的安慰剂安慰剂 CF 中的对照交叉研究。将利用相关的、新颖的结果测量来评估药物效果粘液清除（伽玛闪烁扫描）和气道阻塞（19F-MRI 和 1H-MRI/UTE），此外传统的临床试验终点。这些功能和结构模式的结合应该极大地增强我们对药物对这种异质性肺部疾病的影响的了解。