ABC Heart Fail Cardiomyop 2022; 2(2): 133-135
Heart Transplant from a Genetically-Modified Pig: A Paradigm Shift?
Heart transplant remains the therapy of choice for patients with end-stage heart failure but is limited by chronic shortage of donated organs. Mechanical circulatory support (MCS) devices, with modern designs, have been used as destiny therapy, yielding better results that have positively impacted patient survival. The indications for MCS have significantly increased and become part of the current context of potential candidates for transplant, be it as destiny therapy, bridge-to-transplant or bridge-to candidacy. However, there remains a considerable number of patients who would benefit from the transplant if the availability of donated organs was higher. According to the Brazilian Organ Transplant Association (ABTO), approximately 400 heart transplants are performed yearly in Brazil, but the demand for this procedure is 1,600 per year, i.e., many patients die waiting for an organ.
A possible solution for this issue is xenotransplantation, the process of transplanting organs from other animals, which has gained increasing interest in the last years, for a combination of reasons. First, the efficacy of preclinical models has improved, with an increase in survival time of xenografts. Second, the rapid advances in genome editing, particularly the advent of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats), which allowed the generation of donor pigs with multiple genetic protection modifications; what used to take years can now be done in months, with more accurate and comprehensive results. Third, the spectrum of the porcine endogenous retrovirus (PERV) significantly reduced. There is no evidence of PERV transmission in clinical trials of preclinical models, and novel treatment options and even elimination of these viral diseases are now available. Due to its potential, the importance of xenotransplantation as a solution for the shortage of human organs and tissues remains a great hope for the transplant community, especially for the patients who face advanced disease and high mortality while waiting for a donated heart.
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