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.
Organ transplantation is one of the most advanced health care technologies available and is a last resort therapy to treat failure of a number of different organ systems. There is a growing waiting list of patients who are eligible for transplants but the number of suitable donor organs fall far short of the demand. One important contributor to this shortage results from the fact that many donated organs cannot be used for transplant as there is a very narrow time window during which the organ must be harvested, transported and then transplanted into the recipient. While the organ is outside of the body, it is removed from the normal blood supply and does not receive the supply of oxygen the cells required to survive. As a result, only 17% of the donated lungs could be used for successful transplantation under current medical conditions. Thus, there is a clear unmet medical need for an agent to reduce ischemic damage in organs during transport. We plan to test if recombinant human MG53 protein (rhMG53) can be used to increase the viability of cells in transplanted lungs, a finding that could be developed to greatly expand the current pool of usable organs.