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 theproposed 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.
Thesaurus Terms: Acute Myocardial Infarction;Address;Adjuvant;Animal Model;Area;Biological;Biological Preservation;Blood Circulation;Body System;Cell Membrane;Cell Survival;Cells;Chemistry;Clinical;Clinical Data;Clinical Research;Clinical Trials;Commercialization;Contracts;Development;Drug Formulations;Efficacy Testing;Ex Vivo Perfusion;Failure (Biologic Function);Falls;Family Suidae;Future;Generations;Goals;Harvest;Health Technology;Heart;Hour;Human;Improved;Inflammation;Injury;Ischemia;Joints;Kidney;Label;Laboratories;Large Scale Production;Leadership;Life;Liver;Lung;Lung Injury;Lung Preservation;Lung Transplantation;Maintenance Therapy;Medical;Medical Center;Meetings;Modeling;Names;Neoadjuvant Therapy;Ohio;Operative Surgical Procedures;Organ;Organ Donor;Organ Failure;Organ Harvestings;Organ Preservation;Organ Preservation Solutions;Organ Transplantation;Oxygen;Patients;Perfusion;Phase;Powder Dose Form;Pre-Clinical;Preclinical Study;Preclinical Testing;Preparation;Prevention;Procedures;Process;Protective Effect;Proteins;Protocols Documentation;Public Health Relevance;Quality Control;Recombinants;Research And Development;Research Clinical Testing;Resort;Rodent;Services;Small Business Innovation Research Grant;Solubility;Solutions;Technology;Testing;Time;Tissue Repair;Toxic Effect;Transplant Recipients;Transplantation;Transport Process;Trim Gene;United States;Universities;Vascular Blood Supply;Waiting Lists;
