DENUFOSOL TETRASODIUM INHALATION SOLUTION IN PATIENTS WITH MILD CYSTIC FIBROSIS

地纽福索四钠吸入溶液治疗轻度囊性纤维化患者

• 批准号: 7604984
• 负责人: Theodore Geh-Lu Liou
• 金额: $ 0.6万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7604984
• 关键词: Abnormal ion transport; Agonist; Breathing; Bronchiectasis; Bypass; Chloride Channels; Chloride Ion; Chronic; Class; Computer Retrieval of Information on Scientific Projects Database; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Daily; Development; Disease; Dose; Epithelial; Frequencies; Functional disorder; Funding; Gastrointestinal Diseases; Generations; Genes; Goblet Cells; Grant; Hereditary Disease; INS37217; Inflammation; Institution; Liquid substance; Lung; Mucins; Mucociliary Clearance; Mutation; Nebulizer; P2Y2 receptor; Patients; Placebos; Process; Pulmonary Cystic Fibrosis; Research; Research Personnel; Resources; Respiratory Tract Infections; Respiratory physiology; Safety; Sodium; Solutions; Source; Time; United States National Institutes of Health; Valsava sinus; Week; absorption; airway epithelium; airway surface liquid; apical membrane; base; denufosol tetrasodium; insight; novel; novel strategies; protein function; reproductive

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cystic fibrosis (CF) is a recessive genetic disease, characterized by pulmonary and sinus disease, and gastrointestinal and reproductive tract dysfunction. The disease is caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene, which encodes for an apical membrane epithelial protein that functions as a c-AMP-regulated chloride channel and a regulator of other channels (Boucher, 1994). Defective CFTR results in abnormal ion transport and depleted airway surface liquid volume with reduced mucociliary clearance and a propensity for chronic infection of the respiratory tract with resulting inflammation, progressive airway damage and bronchiectasis. New therapies are being developed for the treatment of CF, based on insights into the pathophysiology of the disease. P2Y2 receptor agonists represent a novel approach to the treatment of CF that attempts to bypass defective CFTR in airway epithelia and, instead, take advantage of the integrated actions of this class of agents on mucociliary clearance that are not dependent on CFTR. These agents act by stimulating the P2Y2 receptor, which results in chloride ion (Cl-) and liquid secretion and the inhibition of sodium (Na+) absorption to hydrate the airway surface liquid layer and create a more normal periciliary fluid milieu,while also stimulating mucin secretion from goblet cells and increasing ciliary beat frequency. Denufosol tetrasodium (INS37217) inhalation solution (denufosol) is a novel second generation, chemically stable, selective P2Y2 receptor agonist under development by InspirePharmaceuticals, Inc. Denufosol may have the ability to restore or maintain mucociliary clearance in patients relatively early in the CF lung disease process, which may preserve lung function and lessen the inevitable repeat cycles of pulmonary bacterial colonization, pulmonary exacerbations, and chronic lung function decline. The objective of this study is evaluate the efficacy, safety and tolerability of a 60 mg nebulizer dose of denufosol compared to placebo when administered three times daily over 24 weeks in patients with mild CF lung disease.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 囊性纤维化（CF）是一种隐性遗传性疾病，以肺和鼻窦疾病以及胃肠道和生殖道功能障碍为特征。该疾病是由囊性纤维化跨膜调节因子（CFTR）基因突变引起的，该基因编码顶端膜上皮蛋白，该蛋白作为c-AMP调节的氯离子通道和其他通道的调节因子发挥作用（Boucher，1994）。缺陷性CFTR导致异常离子转运和耗尽的气道表面液体体积，伴随粘膜纤毛清除率降低和呼吸道慢性感染的倾向，导致炎症、进行性气道损伤和支气管扩张。 基于对该病病理生理学的了解，正在开发用于治疗CF的新疗法。P2 Y2受体激动剂代表了一种治疗CF的新方法，其试图绕过气道上皮中有缺陷的CFTR，而是利用这类药物对不依赖于CFTR的粘膜纤毛清除的综合作用。这些药剂通过刺激P2 Y2受体起作用，这导致氯离子（Cl-）和液体分泌以及抑制钠（Na+）吸收以水合气道表面液体层并产生更正常的纤毛周围流体环境，同时还刺激杯状细胞的粘蛋白分泌并增加纤毛搏动频率。Denufosol tetrasylate（INS 37217）吸入溶液（denufosol）是一种新型第二代、化学稳定、选择性P2 Y2受体激动剂，由InspirePharmaceuticals，Inc.开发。地努福索可能具有在CF肺病过程中相对早期恢复或维持患者的粘膜纤毛清除的能力，这可能保护肺功能并减少肺细菌定植、肺恶化和慢性肺功能下降的不可避免的重复周期。 本研究的目的是评估60 mg雾化剂剂量的地努福索与安慰剂相比，在24周内每天给药3次，治疗轻度CF肺病患者的疗效、安全性和耐受性。