Increasing viability of lung organs for transplantation

描述(申请人提供)：虽然器官移植是治疗肺部终末器官衰竭患者的关键的最后手段，但由于合适的捐献器官的数量远远不能满足这些挽救生命的程序的需求，有资格接受移植的患者的等待名单越来越多。改善捐赠器官的保存，以便更大比例的器官仍可用于移植程序，是美国尚未得到满足的医疗需求的一个重要领域。一种减少运输过程中器官缺血性损害的试剂将代表一种技术，它将加强对现有捐赠者的保护，扩大手术实施的时间窗口，并有可能使可随后移植的边缘器官复苏。这项应用的目的是研究一种名为MG53的组织修复蛋白在肺移植器官保存中的使用。Trim-edicine的研究和开发工作已经证实，重组人MG53蛋白(RhMG53)在预防和保护细胞膜损伤方面具有巨大的潜力。在啮齿动物和大型动物模型研究中，有广泛的证据支持rhMG53对肺、心脏和肾脏的缺血性损伤的保护作用，为使用rhMG53进行器官保存提供了理由。重组人MG53可作为移植手术前诱导治疗的辅助剂，或应用于移植治疗后保护器官功能的维持治疗。因此，在移植过程中使用rhMG53作为一种成分来延长器官的使用寿命是这种蛋白质吸引人的第一个标签。我们期待着实现这一目标 在这一阶段的SBIR应用中提出的研究将使我们能够与FDA联系，寻求将rhMG53推向临床试验的指导。该项目将涉及Trim-edicine和俄亥俄州立大学韦克斯纳医学中心综合移植中心之间的联合开发工作。我们建议的研究将包含两个目标。第一个目标是生产足够的重组人MG53蛋白用于临床前研究，并在现有的器官保存溶液中测试配方。第二个目的是利用猪体外肺灌流(EVLP)模型确定rhMG53对肺损伤的保护作用。

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.