Increasing viability of lung organs for transplantation

描述（由申请人提供）：虽然器官移植是治疗肺终末器官衰竭患者的重要最后手段，但由于合适的供体器官数量远远不能满足这些救命手术的需求，因此有资格接受移植的患者的等待名单不断增加。改善捐献器官的保存，使更大比例的器官仍能用于移植手术，这是美国未满足的医疗需求的一个重要领域。一种在运输过程中减少器官缺血性损伤的试剂将代表一种技术，该技术将增强对现有供体的保护，扩大手术实施的时间窗口，并可能使边缘器官复苏，然后可以移植。本申请的目的是检查名为MG 53的组织修复蛋白在肺移植的器官保存中的用途。TRIM-medicine的研究和开发工作已经确定，重组人MG 53蛋白（rhMG 53）在预防和保护细胞膜损伤方面具有巨大的潜力。有大量证据支持rhMG 53在啮齿动物和大型动物模型研究中保护肺、心脏和肾脏缺血性损伤的有效性，为rhMG 53用于器官保存提供了依据。rhMG 53可潜在地用作移植手术前诱导治疗的辅助剂或用于移植治疗后保护器官功能的维持治疗。因此，使用rhMG 53作为移植过程中延长器官使用寿命的成分是这种蛋白质的第一个有吸引力的标签。我们期待着实现 在这项1期SBIR申请中提出的研究将使我们能够与FDA联系，寻求将rhMG 53推向临床试验的指导。该项目将涉及TRIM-medicine和俄亥俄州州立大学Wexner医学中心的综合移植中心之间的联合开发工作。我们建议的研究应包含两个目标。第一个目标是生产足够的rhMG 53蛋白，用于临床前研究和现有器官保存溶液中的测试制剂。第二个目的将使用猪离体肺灌注（EVLP）模型确定rhMG 53在保护肺损伤中的功效。

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.