Increasing viability of lung organs for transplantation

提高肺器官移植的活力

• 批准号: 8779805
• 负责人: Zelin Sheng
• 金额: $ 30万
• 依托单位: TRIM-EDICINE, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8779805
• 关键词: Acute myocardial infarction; Address; Adjuvant; Animal Model; Area; Biological; Biological Preservation; Blood Circulation; Cell Survival; Cell membrane; Cells; Chemistry; Clinical; Clinical Data; Clinical Research; Clinical Trials; Contracts; Development; Drug Formulations; Failure; Family suidae; Future; Generations; Goals; Harvest; Health Technology; Heart; Hour; Human; Inflammation; Injury; Ischemia; Joints; Kidney; Label; Laboratories; Leadership; Life; Liver; Lung; Lung Transplantation; Maintenance Therapy; Medical; Medical center; Modeling; Names; Neoadjuvant Therapy; Ohio; Operative Surgical Procedures; Organ; Organ Donor; Organ Harvestings; Organ Preservation; Organ Preservation Solutions; Organ Transplantation; Organ failure; Oxygen; Patients; Perfusion; Phase; Powder dose form; Preclinical Testing; Preparation; Prevention; Procedures; Process; Proteins; Protocols documentation; Quality Control; Recombinants; Resort; Rodent; Services; Small Business Innovation Research Grant; Solubility; Solutions; TRIM Gene; Technology; Testing; Time; Toxic effect; Transplant Recipients; Transplantation; Transport Process; United States; Universities; Vascular blood supply; Waiting Lists; body system; commercialization; efficacy testing; ex vivo perfusion; falls; improved; large scale production; lung injury; lung preservation; meetings; pre-clinical; preclinical study; protective effect; public health relevance; research and development; research clinical testing; tissue repair

DESCRIPTION (provided by applicant): While organ transplantation is a vital last resort therapy to treat patients with end-organ failure of the lung there is a growing waiting list of patients who are eligible for transplants as the number of suitable donor organs fall far short of the demand for these lifesaving procedures. Improving the preservation of donated organs so that a greater percentage would remain viable for use in transplant procedures represents an important area of unmet medical need in the United States. An agent to reduce ischemic damage to organs during transport will represent a technology that would enhance the protection of existing donors, expand the time window for surgical implementation, and potentially resuscitate marginal organs which could then be transplanted. The goal of this application is to examine the use of a tissue repair protein named MG53 in organ preservation for lung transplantation. Research and development efforts at TRIM-edicine have established that the recombinant human MG53 protein (rhMG53) has great potential in prevention and protection of injuries to the cell membrane. There is extensive evidence to support the efficacy for rhMG53 in protecting ischemic damage to the lung, heart and kidney in rodent and large animal model studies, providing the justification for the use of rhMG53 in organ preservation. rhMG53 can potentially be used as adjuvant for induction therapy prior to transplant surgery or applied in maintenance therapy for protection of organ function after transplant therapy. As a result, the use of rhMG53 as an ingredient to extend the useful life of organs during transplantation is an appealing first label for this protein. We anticipate that fulfillment of the proposed studies in this Phase 1 SBIR application will enable us to approach FDA to seek guidance on moving rhMG53 toward clinical trials. This project will involve joint development efforts between TRIM-edicine and the Comprehensive Transplant Center at Ohio State University Wexner Medical Center. Our proposed studies shall contain two aims. The first aim will produce sufficient rhMG53 protein for preclinical studies and test formulation in existing organ preservation solutions. The second aims will determine the efficacy for rhMG53 in protection of lung injury using the porcine ex vivo lung perfusion (EVLP) model.

描述（由申请人提供）：虽然器官移植是治疗肺最终器官衰竭患者的至关重要的措施，但由于合适的供体器官数量的数量远远远远远远远未达到这些救生程序的需求，因此越来越多的等待患者有资格进行移植。改善捐赠器官的保存，以便在移植程序中使用更大的比例将是美国未满足医疗需求的重要领域。在运输过程中减少缺血性损害的代理将代表一项技术，该技术将增强现有捐助者的保护，扩大手术实施的时间窗口，并有可能复苏的边际器官可以移植。该应用的目的是检查在器官保存中使用的组织修复蛋白用于肺移植。修剪氨基氨酸的研发工作已经确定，重组人MG53蛋白（RHMG53）在预防和保护细胞膜的损伤方面具有巨大的潜力。有大量证据支持RHMG53在啮齿动物和大型动物模型研究中保护肺，心脏和肾脏的缺血性损害的功效，从而为在器官保存中使用RHMG53提供了理由。 RHMG53可能在移植手术前可能用作诱导治疗的辅助治疗，或用于维护治疗以保护移植治疗后的器官功能。结果，将RHMG53用作延长移植过程中器官使用寿命的成分是该蛋白质的吸引人的首个标签。我们预计实现 在此阶段1 SBIR应用中提出的研究将使我们能够接触FDA，以寻求将RHMG53转向临床试验的指导。该项目将涉及俄亥俄州立大学韦克斯纳医学中心的培养基和综合移植中心之间的联合发展工作。我们提出的研究应包含两个目标。第一个目的将产生足够的RHMG53蛋白，用于临床前研究和测试配方。第二个目标将确定RHMG53使用猪外肺灌注（EVLP）模型保护肺损伤的功效。