Refanalin for lung preservation and transplantation

Refanalin 用于肺保存和移植

• 批准号: 7537838
• 负责人: WEIZHONG CAI
• 金额: $ 95.72万
• 依托单位: ANGION BIOMEDICA CORPORATION
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7537838
• 关键词: 3-Dimensional; Acute; Address; Affect; Allografting; Alveolar; Animal Model; Apoptosis; Attenuated; Binding Sites; Biological Assay; Biological Preservation; Biological Products; Biology; Canis familiaris; Caring; Cell Death; Cessation of life; Clinical; Clinical Trials; Cryopreservation; Data; Data Analyses; Dependence; Depth; Development; Dose; Drug Design; Epithelial; Epithelial Cells; Evaluation; Experimental Models; Failure; Functional disorder; Funding; Gene Proteins; Genes; Goals; Growth Factor; Growth Factor Gene; Half-Life; Head; Heart; Heart Arrest; Heart-Lung Transplantation; Hepatocyte Growth Factor; Human; Immune; In Vitro; Incidence; Industry; Infiltration; Inflammatory Response; Injury; International; Ischemia; Kentucky; Kidney Transplantation; Knowledge; Laboratories; Length; Liver; Lung; Lung Transplantation; Lung diseases; Modality; Modeling; Molecular Weight; Morbidity - disease rate; Natural regeneration; Necrosis; North Carolina; Numbers; Operative Surgical Procedures; Organ; Organ Donor; Organ Preservation; Organ Transplantation; Outcome; Paper; Pathway interactions; Patients; Phage Display; Phase; Physiological reperfusion; Pre-Clinical Model; Preservation Technique; Progress Reports; Proteins; Proteomics; Proto-Oncogene Protein c-met; Public Health; Range; Rattus; Refractory; Reperfusion Injury; Reperfusion Therapy; Reporting; Research; Research Design; Resources; Respiratory physiology; Retrieval; Risk; Rodent Model; Safety; Schedule; Scientist; Secondary to; Series; Serious Adverse Event; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Societies; Solid; Solutions; Staging; Standards of Weights and Measures; Supervision; Testing; Therapeutic; Time; Tissues; Today; Training; Translational Research; Transplant Surgeon; Transplantation; Treatment Protocols; United States Food and Drug Administration; United States National Institutes of Health; Universities; Washington; Wisconsin; Work; aged; base; clinically relevant; clinically significant; cost; design; drug development; drug discovery; drug efficacy; efficacy trial; expectation; experience; graft function; healthy volunteer; human MET protein; improved; in vivo Model; innovation; lung injury; lung ischemia; lung preservation; medical schools; mimetics; molecular modeling; mortality; novel; pharmacophore; pre-clinical; prevent; professor; programs; pulmonary function; repaired; small molecule; symposium

DESCRIPTION (provided by applicant): Lung transplantation is the only effective treatment modality for patients with end-stage lung disease. Ischemia-reperfusion injury, associated with the retrieval, storage and transplantation of the lung is a major immune-independent factor adversely affecting early graft function, graft viability and recipient morbidity and mortality. Marginal donor lungs, are even more susceptible to ischemia-reperfusion injury, and often fail transplantation. Scatter factor/hepatocyte growth factor has significant protective activity in the setting of pulmonary ischemia-reperfusion injury and additionally, favors pulmonary epithelial repair and regeneration. However its clinical use is limited by the logistical difficulties associated with its administration. During our Phase I program, we have identified Refanalin, an organic small molecule scatter factor/hepatocyte growth factor mimetic that improves lung function secondary to ischemia-reperfusion injury, attenuates pulmonary epithelial death and promotes epithelial regeneration. In a preclinical model of lung cold preservation and transplantation, Refanalin treatment reduced roentgenographic alveolar infiltration, improved pulmonary function and preserved pulmonary microarchitecture. The present Phase II makes an in-depth evaluation of Refanalin efficacy in clinically relevant models of lung transplantation. By attenuating allograft dysfunction and preventing allograft failure, Refanalin can reduce recipient morbidity and mortality. By attenuating ischemia- reperfusion injury in the marginal lung, Refanalin can salvage an otherwise discarded organ, and increase the donor pool. PUBLIC HEALTH RELEVANCE: A small molecule cytoprotective that can be added to the lung preservation solution and administered to graft recipient has significant clinical potential in lung and other solid organ transplantation.

描述(申请人提供)：肺移植是终末期肺部疾病患者唯一有效的治疗方式。与肺的恢复、储存和移植相关的缺血再灌注损伤是影响早期移植物功能、移植物存活率、受体发病率和死亡率的一个主要的免疫非依赖性因素。边缘供体肺更容易受到缺血再灌注损伤的影响，常常移植失败。分散因子/肝细胞生长因子在肺缺血再灌注损伤中具有明显的保护作用，并有利于肺上皮细胞的修复和再生。然而，它的临床应用受到与其给药相关的后勤困难的限制。在我们的第一阶段计划中，我们已经确定了Refanalyin，一种有机小分子分散因子/肝细胞生长因子模拟物，可以改善缺血再灌注损伤后的肺功能，减轻肺上皮细胞死亡，并促进上皮细胞再生。在肺冷保存和移植的临床前模型中，Refanalyin治疗减少了X线片中的肺泡渗透，改善了肺功能，并保存了肺微结构。目前的第二阶段对瑞法林在肺移植临床相关模型中的疗效进行了深入的评估。通过减轻同种异体移植物功能障碍和预防同种异体移植失败，瑞法林可以降低受体的发病率和死亡率。通过减轻边缘肺的缺血再灌注损伤，Refanalyin可以挽救原本被丢弃的器官，并增加捐赠者的储备。公共卫生相关性：一种可以添加到肺保存液中并用于移植受者的小分子细胞保护性物质在肺和其他固体器官移植中具有显著的临床潜力。