Development of BIO 300 as a MCM for lethal radiation pneumonitis/fibrosis

开发 BIO 300 作为致命放射性肺炎/纤维化的 MCM

基本信息

批准号：
9201938
负责人：
Isabel Lauren Jackson
金额：
$ 29.9万
依托单位：
HUMANETICS CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9201938
关键词：
Acute Address Adult Respiratory Distress Syndrome Advanced Development Animal Model Animals Anti-Inflammatory Agents Anti-inflammatory Antioxidants Area Under Curve Baltimore Biological Availability Blood Body Weight Bone Marrow C57L/J Mouse Caliber Cell Cycle Cell Cycle Progression Cells Characteristics Chest Chronic DNA Damage Data Development Development Plans Dose Drug Kinetics Evaluation Exposure to FDA approved Face Fibrosis Filgrastim Formulation Free Radicals Future Genistein Goals Granulocyte Colony-Stimulating Factor Hematopoietic Histopathology Human Individual Inflammatory Injury Legal patent Lethal Dose 50 Licensure Life Link Lung Maryland Mediating Medical Modeling Morbidity - disease rate Mus Nuclear Accidents Oral Oral Administration Organ Organ failure Particle Size Pegfilgrastim Pharmaceutical Preparations Play Positioning Attribute Prevention Property Protein Tyrosine Kinase Pulmonary Fibrosis Pulmonary Inflammation Radiation Radiation Injuries Radiation Pneumonitis Radioprotection Rattus Reaction Recombinants Recording of previous events Regimen Rodent Model Role Safety Self-Administered Signal Pathway Signal Transduction Pathway Structure of parenchyma of lung Supervision Supportive care Suspension substance Suspensions Syndrome Terrorism Therapeutic Time Tissues Toxicokinetics Translating Tyrosine Kinase Inhibitor Universities Weight Whole-Body Irradiation Work animal efficacy animal rule cancer radiation therapy course development cytokine therapy drug development effective therapy efficacy testing efficacy trial experience gastrointestinal gender difference improved interest irradiation knowledge base liquid formulation lung injury medical schools mortality nanoparticle oxidative damage preclinical study prevent pulmonary function radiation effect repaired research and development respiratory response

Acute Address Adult Respiratory Distress Syndrome Advanced Development Animal Model Animals Anti-Inflammatory Agents Anti-inflammatory Antioxidants Area Under Curve Baltimore Biological Availability Blood Body Weight Bone Marrow C57L/J Mouse Caliber Cell Cycle Cell Cycle Progression Cells Characteristics Chest Chronic DNA Damage Data Development Development Plans Dose Drug Kinetics Evaluation Exposure to FDA approved Face Fibrosis Filgrastim Formulation Free Radicals Future Genistein Goals Granulocyte Colony-Stimulating Factor Hematopoietic Histopathology Human Individual Inflammatory Injury Legal patent Lethal Dose 50 Licensure Life Link Lung Maryland Mediating Medical Modeling Morbidity - disease rate Mus Nuclear Accidents Oral Oral Administration Organ Organ failure Particle Size Pegfilgrastim Pharmaceutical Preparations Play Positioning Attribute Prevention Property Protein Tyrosine Kinase Pulmonary Fibrosis Pulmonary Inflammation Radiation Radiation Injuries Radiation Pneumonitis Radioprotection Rattus Reaction Recombinants Recording of previous events Regimen Rodent Model Role Safety Self-Administered Signal Pathway Signal Transduction Pathway Structure of parenchyma of lung Supervision Supportive care Suspension substance Suspensions Syndrome Terrorism Therapeutic Time Tissues Toxicokinetics Translating Tyrosine Kinase Inhibitor Universities Weight Whole-Body Irradiation Work animal efficacy animal rule cancer radiation therapy course development cytokine therapy drug development effective therapy efficacy testing efficacy trial experience gastrointestinal gender difference improved interest irradiation knowledge base liquid formulation lung injury medical schools mortality nanoparticle oxidative damage preclinical study prevent pulmonary function radiation effect repaired research and development respiratory response

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项目摘要

Project Summary A significant need exists for effective medical countermeasures for radiation-induced pneumonitis and pulmonary fibrosis associated with the delayed effects of acute radiation exposure. Of great importance are countermeasures that can be distributed for use without medical supervision, making orally effective countermeasures of high interest and importance. To address this unmet need, Humanetics Corporation is developing BIO 300 Oral Suspension (active ingredient genistein) to treat the delayed effects of acute radiation exposure (DEARE) in the lung. Genistein, a non-specific tyrosine kinase inhibitor, has a strong history of safety, and has substantial radioprotective effects linked to its strong antioxidant capacity, anti-inflammatory properties, and its effects on cell cycle division. In preclinical studies summarized in this proposal BIO 300 has been shown to significantly improve survival, mitigate lung tissue injury, and improve pulmonary function following whole thoracic lung irradiation. The aim of this proposal is to determine the optimum therapeutic dosing regimen of BIO 300 to reduce lung damage and maximize the likelihood for survival following acute radiation exposure to the thoracic region. Models in which the dose response and timecourse of radiation induced pulmonary damage are well defined will be used in the proposed studies. Studies are also proposed to further understand the effect that total or partial body irradiation has on BIO 300’s pharmacokinetic properties. The overall goal of the proposed studies is to advance the development of BIO 300 as a medical countermeasure towards FDA approval. The proposed work builds on the R&D experience of Humanetics Corporation toward the development of BIO 300 as a medical countermeasure for acute radiation exposure. The main emphasis of future development will be to move BIO 300 development into large animal efficacy testing to determine if the positive efficacy data observed in the rodent model translates to a larger animal. Continued development of BIO 300 will undoubtedly expand the scientific knowledge base and support the continued evaluation and development of agents to prevent and/or treat the acute and chronic effects of radiation exposure. Moreover, with BIO 300’s advanced development as a medical radiation countermeasure, and as an adjunct to cancer radiotherapy, it presents an opportunity for an accelerated development course through pivotal efficacy trials and to licensure.

项目摘要对于辐射引起的肺炎和肺纤维化与急性辐射暴露的延迟作用有关。伟大重要性是可以在没有医疗监督的情况下分发用于使用的对策口头有效的对策，具有高兴趣和重要性。为了满足这种未满足的需求，人类材料公司正在开发生物300口服悬浮液（主动成分染料木黄酮）来治疗肺中急性辐射暴露（DEARE）的延迟作用。染料木黄酮，一种非特异性酪氨酸激酶抑制剂具有很强的安全史，并且具有与其相关的实质性辐射保护作用强抗氧化能力，抗炎特性及其对细胞周期分裂的影响。在临床前研究总结了本提案生物300的临床研究可显着改善整个胸腔肺后，生存，减轻肺组织损伤并改善肺功能辐照。该提案的目的是确定生物300的最佳治疗剂量方案急性辐射暴露后，减少肺损伤并最大化生存的可能性胸部区域。辐射诱导肺的剂量反应和时间科学的模型损害的定义良好将用于拟议的研究。还提出了进一步的研究了解总体或部分身体辐照对生物300的药代动力学特性的影响。拟议研究的总体目标是推进生物300作为医学的发展对FDA批准的对策。拟议的工作以研发经验为基础人类宗教公司开发生物300，以作为急性的医学对策辐射暴露。未来发展的主要重点是移动Bio 300开发进行大型动物效率测试，以确定在啮齿动物模型中观察到的正效率数据是否转化为更大的动物。 Bio 300的持续开发无疑将扩大科学知识库和支持代理的持续评估和开发，以预防和/或治疗辐射暴露的急性和慢性作用。此外，Bio 300的高级作为医疗辐射的对策，作为癌症放射疗法的辅助通过关键效率试验为加速发展课程提供了机会许可证。