A Therapeutic for Radiation Induced Lung Injury

辐射引起的肺损伤的治疗方法

基本信息

批准号：
8647618
负责人：
LATHA PAKA
金额：
$ 29.99万
依托单位：
ANGION BIOMEDICA CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-05-15 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8647618
关键词：
Accidents Acute Acute Lung Injury Animals Area Bioavailable Biochemical Breathing Canis familiaris Cardiac Cells Chest Chronic Clinic Clinical Management Data Dose Drug Formulations Endothelial Cells Epithelial Cells Evaluation Event Exposure to Feasibility Studies Fibrosis Growth Factor Health Hepatocyte Growth Factor In Vitro Inflammation Injury Interstitial Lung Diseases Ionizing radiation Kidney Laboratories Length Lung Maryland Medical Mesenchymal Modeling Morbidity - disease rate Mus Nuclear Accidents Oral Oral Administration Organ Pathway interactions Phase Phase I Clinical Trials Pilot Projects Pneumonia Population Proteins Pulmonary Fibrosis Radiation Radiation Injuries Radiation Pneumonitis Radioisotopes Research Research Design Risk Route Safety Sampling Sheep Small Business Innovation Research Grant Source Specialized Center Structure of parenchyma of lung Terrorism Therapeutic Therapeutic Effect Therapeutic Intervention Time Tissues United States Food and Drug Administration Universities Up-Regulation War animal rule base drug candidate efficacy trial gene therapy help-seeking behavior in vivo irradiation laboratory facility lung injury mass casualty meetings mimetics mortality novel therapeutic intervention paracrine phase 2 study protective effect public health relevance receptor receptor expression safety study small molecule

项目摘要

DESCRIPTION (provided by applicant): Nuclear accidents and terrorism present a serious threat for causing mass-casualty scenarios. In radiation events, many people receive non-uniform whole-body or partial-body irradiation. The risk of exposure to ionizing radiation due to terrorist activities could result in acute injury as well as long-term adverse health effects in thousands of people. The lung is one of the more radiosensitive organs and inhaling large quantities of radionuclides produces a spectrum of severe functional and morphological changes, ranging from radiation pneumonitis and pulmonary fibrosis. Although efforts to find suitable radiation countermeasures were initiated more than 50 years ago, no safe and effective radiation countermeasure has been approved by the Food and Drug Administration (FDA). Thus, there is a pressing need for radiation countermeasures. Hepatocyte growth factor (HGF) is a paracrine growth factor produced by cells of mesenchymal origin; Activation of the HGF pathway is pulmonary protective and reparative and HGF therapy mitigates lung injury via its c-Met receptor expressed in epithelial and endothelial cells. HGF also protects against fibrotic remodeling following lung injury. HGF protein or gene therapy, however, is not a viable treatment approach especially in a mass casualty setting. BB3 is our first-in-class, bioavailable small molecule HGF mimetic. It has completed Phase I clinical trials and is currently in Phase II safety and efficacy trials for renal and cardiac indications. Our studies are designed to develop BB3 as an effective mitigator of radiation injury by performing the efficacy studies in radiation-induced pneumonitis and pulmonary fibrosis models. These studies are critical for subsequent SBIR phase II studies with the ultimate objective of developing an effective medical countermeasure to use in the clinic.

描述（由申请人提供）：核事故和恐怖主义对造成群众休闲情景的严重威胁。在辐射事件中，许多人会接受全身或部分体型辐射。由于恐怖活动而导致的电离辐射的风险可能会导致急性伤害以及成千上万人的长期不良健康影响。肺是最放射敏感的器官之一，吸入大量放射性核素会产生各种严重的功能和形态变化，范围从辐射肺炎和肺纤维化。尽管在50年前开始了寻找合适的辐射对策的努力，但食品药品监督管理局（FDA）尚未批准安全有效的辐射对策。因此，迫切需要辐射对策。肝细胞生长因子（HGF）是间质起源细胞产生的旁分泌生长因子。 HGF途径的激活是肺部保护性和修复性，HGF治疗通过其上皮细胞和内皮细胞表达的C-MET受体减轻肺损伤。 HGF还可以防止肺部损伤后的纤维化重塑。但是，HGF蛋白或基因治疗并不是一种可行的治疗方法，尤其是在大规模伤亡环境中。 BB3是我们的第一类生物利用小分子HGF模拟物。它已经完成了I期临床试验，目前正在肾脏和心脏适应症的II期安全和功效试验中。我们的研究旨在通过在辐射诱导的肺炎和肺纤维化模型中进行功效研究来发展BB3作为放射线损伤的有效缓解剂。这些研究对于随后的SBIR II期研究至关重要，其最终目标是开发有效的医学对策以在诊所使用。