MSGID: 1:317/3 649fabf5   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    Lessons learned from first genetically-modified pig heart into human   
   patient    
      
     Date:   
         June 30, 2023   
     Source:   
         University of Maryland School of Medicine   
     Summary:   
         A new study has revealed the most extensive analysis to date on what   
         led to the eventual heart failure in the world's first successful   
         transplant of a genetically-modified pig heart into a human patient.   
      
      
         Facebook Twitter Pinterest LinkedIN Email   
      
   ==========================================================================   
   FULL STORY   
   ==========================================================================   
   A new study published today in The Lancet has revealed the most extensive   
   analysis to date on what led to the eventual heart failure in the world's   
   first successful transplant of a genetically-modified pig heart into a   
   human patient.   
      
   This groundbreaking procedure was conducted by University of Maryland   
   School of Medicine (UMSOM) physician-scientists back in January 2022   
   and marked an important milestone for medical science.   
      
   The patient, 57-year-old David Bennett, Sr., was treated at the University   
   of Maryland Medical Center. He experienced strong cardiac function with   
   no obvious signs of acute rejection for nearly seven weeks after the   
   surgery. A sudden onset of heart failure led to his death two months   
   after the transplant. Since then, the transplant team has been conducting   
   extensive studies into the physiologic processes that led to the heart   
   failure to identify factors that can be prevented in future transplants   
   to improve the odds of longer-term success.   
      
   "Our paper provides crucial insight into how a multitude of factors likely   
   played a role in the functional decline of the transplanted heart,"   
   said study lead author Muhammad M. Mohiuddin, MD, Professor of Surgery   
   and Scientific/ Program Director of the Cardiac Xenotransplantation   
   Program at UMSOM. "Our goal is to continue moving this field forward as   
   we prepare for clinical trials of xenotransplants involving pig organs."   
   Mr. Bennett, who was in end-stage heart failure and nearing the end   
   of his life, did not qualify for a traditional heart transplant. The   
   procedure was authorized by the U.S. Food and Drug Administration under   
   its expanded access (compassionate use) provision.   
      
   "We were determined to shed light on what led to the heart transplant   
   dysfunction in Mr. Bennett, who performed a heroic act by volunteering   
   to be the first in the world," said study co-author Bartley Griffith, MD,   
   Professor of Surgery and The Thomas E. and Alice Marie Hales Distinguished   
   Professor in Transplantation at UMSOM. "We want our next patient to not   
   only survive longer with a xenotransplant but to return to normal life   
   and thrive for months or even years."  To better understand the processes   
   that led to dysfunction of the pig heart transplant, the research team   
   performed extensive testing on the limited available tissues in the   
   patient. They carefully mapped out the sequence of events that led to   
   the heart failure demonstrating that the heart functioned well on imaging   
   tests like echocardiography until day 47 after surgery.   
      
   The new study confirms that no signs of acute rejection occurred during   
   the first several weeks after the transplant. Likely, several overlapping   
   factors led to heart failure in Mr. Bennett, including his poor state   
   of health prior to the transplant that led him to become severely   
   immunocompromised. This limited the use of an effective anti-rejection   
   regimen used in preclinical studies for xenotransplantation. As a   
   result, the researchers found, the patient was likely more vulnerable   
   to rejection of the organ from antibodies made by the immune system. The   
   researchers found indirect evidence of antibody- mediated rejection based   
   on histology, immunohistochemical staining and single cell RNA analysis.   
      
   The use of an intravenous immunoglobulin, IVIG, a drug that contains   
   antibodies, may also have contributed to damage to the heart muscle   
   cells. It was given to the patient twice during the second month after the   
   transplant to help prevent infection, likely also triggering an anti-pig   
   immune response. The research team found evidence of immunoglobulin   
   antibodies targeting the pig vascular endothelium layer of the heart.   
      
   Lastly, the new study investigated the presence of a latent virus,   
   called porcine cytomegalovirus (PCMV), in the pig heart, which may have   
   contributed to the dysfunction of the transplant. Activation of the   
   virus may have occurred after the patient's anti-viral treatment regimen   
   was reduced to address other health issues. This may have initiated an   
   inflammatory response causing cell damage. However, there is no evidence   
   that the virus infected the patient or spread to organs beyond the   
   heart. Improved PCMV testing protocols have been developed for sensitive   
   detection and exclusion of latent viruses for future xenotransplants.   
      
   Other UMSOM faculty co-authors of this study include: Avneesh K Singh,   
   PhD, Alison Grazioli, MD, Kapil Saharia, MD, Tianshu Zhang, MD, and   
   Christine Lau, MD.   
      
   "Valuable lessons can be learned from this groundbreaking surgery and   
   the courageous first patient, Mr. Bennett, that will better inform   
   us for future xenotransplants," said UMSOM Dean Mark T. Gladwin, MD,   
   Vice President for Medical Affairs, University of Maryland, Baltimore,   
   and the John Z. and Akiko K. Bowers Distinguished Professor. "In the   
   future, our team of surgeon- scientists will utilize newly designed   
   immune cell assays to monitor the patient more precisely in the days,   
   weeks, and months following the xenotransplant. This will provide   
   stricter control of the earliest signs of rejection and the promise   
   of a truly lifesaving innovation."  Disclosures: Members of Program   
   in Cardiac Xenotransplantation at UMSOM received research funding from   
   United Therapeutics Corporation. Revivicor, Inc., provided the pigs, and   
   Kiniksa Pharmaceuticals provided anti-CD40 antibodies. The University   
   of Maryland School of Medicine and the University of Maryland Medical   
   Center supported the remaining costs.   
      
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Heart_Disease # Diseases_and_Conditions #   
                   Stroke_Prevention # Today's_Healthcare   
             o Plants_&_Animals   
                   # Virology # Biology # Veterinary_Medicine # Biotechnology   
       * RELATED_TERMS   
             o Face_transplant o Genetically_modified_food o Heart_rate o   
             Artificial_heart o Heart_failure o Coronary_heart_disease o   
             Ischaemic_heart_disease o CPR   
      
   ==========================================================================   
   Story Source: Materials provided by   
   University_of_Maryland_School_of_Medicine. Note: Content may be edited   
   for style and length.   
      
      
   ==========================================================================   
   Journal Reference:   
      1. Muhammad M Mohiuddin, Avneesh K Singh, Linda Scobie, Corbin   
      E Goerlich,   
         Alison Grazioli, Kapil Saharia, Claire Crossan, Allen Burke,   
         Cinthia Drachenberg, Cihan Oguz, Tianshu Zhang, Billeta Lewis,   
         Alena Hershfeld, Faith Sentz, Ivan Tatarov, Sarah Mudd, Gheorghe   
         Braileanu, Kathryn Rice, John F Paolini, Kent Bondensgaard, Todd   
         Vaught, Kasinath Kuravi, Lori Sorrells, Amy Dandro, David Ayares,   
         Christine Lau, Bartley P Griffith.   
      
         Graft dysfunction in compassionate use of genetically engineered   
         pig-to- human cardiac xenotransplantation: a case report. The   
         Lancet, 2023; DOI: 10.1016/S0140-6736(23)00775-4   
   ==========================================================================   
      
   Link to news story:   
   https://www.sciencedaily.com/releases/2023/06/230630123122.htm   
      
   --- up 1 year, 17 weeks, 4 days, 10 hours, 50 minutes   
    * Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)   
   SEEN-BY: 15/0 106/201 114/705 123/120 153/7715 218/700 226/30 227/114   
   SEEN-BY: 229/110 112 113 307 317 400 426 428 470 664 700 291/111 292/854   
   SEEN-BY: 298/25 305/3 317/3 320/219 396/45 5075/35   
   PATH: 317/3 229/426