SpankyMcFarland Posted January 15, 2022 Report Share Posted January 15, 2022 On January 7, a 57 year old man with terminal cardiac failure underwent a nine hour operation at the University of Maryland School of Medicine and received a cardiac transplant from a pig. Three innovations made this historic procedure possible: 1. Genetic modification. Ten genes were changed in the pig: three were removed that would have caused a rapid, antibody-mediated rejection of the foreign organ; one was removed that would have made the heart too big; and six human genes were added to reduce inflammation, rejection and blood coagulation. 2. A perfusion solution to keep the porcine heart in optimal condition between operations. Apparently, this product contains cocaine which caused a regulatory headache for the researchers. 3. A powerful drug, KPL-404, that suppresses the body’s immunological reaction (in particular, CD-40) to the foreign organ. The potential significance is enormous - many thousands die every year awaiting organ transplantation form human donors and demand will only increase - but there’s an army of potential problems ahead. One expert called the patient ‘courageous’ which is not something you want to hear. On the medical side, rejection and infection are the two big immediate dangers. Rejection comes in three basic types - hyperacute, acute and chronic. The hyperacute stage seems to have been successfully navigated but the body has a myriad of responses to foreign antigens that are not fully understood. An infection is made more likely because of the immunosuppressive medication the patient is on. This could be any extrinsic infectious agent or might have travelled in the transplanted organ itself. Longer term, one has to wonder how a heart from a quadruped will perform pumping blood all the way up to the head in a biped. Not a major worry right now. There are ethical issues. If the patient dies in the next few weeks the decision to go ahead will be questioned; this is an experimental treatment and I’d say the surgical team are not getting much sleep at the moment. Some people may have concerns about any animal transplants to humans. There are also those may be put off specifically by a pig donor for religious reasons. Dr. Mohiuddin addressed this issue directly. The patient was denied a human transplant partly because of his poor compliance with treatment recommendations in the past, including management of hypertension. One aspect of the story dominating coverage at the moment is that the patient did time for a serious assault and the family of the victim are asking why a person guilty of a serious felony deserves such expensive care. Doctors would say they treat anybody regardless of their past. https://www.dicardiology.com/videos/video-details-first-pig-heart-transplant-surgery-human 1 Quote Link to comment Share on other sites More sharing options...
eyeball Posted January 15, 2022 Report Share Posted January 15, 2022 1 hour ago, SpankyMcFarland said: Some people may have concerns about any animal transplants to humans. There are also those may be put off specifically by a pig donor for religious reasons. Harp seals have been suggested as an alternative to pigs for heart valves but I imagine they're a long ways off from being able to use the entire heart. An abundance of controversy of course surrounds the issue. https://www.cmaj.ca/content/180/13/1290 Quote Animal rights groups say the research is unnecessary and will serve only as a government propaganda tool to promote Canada’s sealing industry, which received a major blow on May 5 when Europe banned imports of seal products. The federal government projects that a commercial seal valve market could generate substantial revenue for Canada, but heart valve experts involved in the project say the research could lead to more than just financial gain. If their theory is proven true — if seal valves do offer significant advantages over existing bioprosthetic valves — the research could result in prolonged and improved lives for sufferers of heart valve disease. “I’m optimistic that it could be superior to bovine or porcine valves,” says Philippe Pibarot, Canada research chair in valvular heart diseases. 1 Quote Link to comment Share on other sites More sharing options...
SpankyMcFarland Posted January 15, 2022 Author Report Share Posted January 15, 2022 (edited) 33 minutes ago, eyeball said: Harp seals have been suggested as an alternative to pigs for heart valves but I imagine they're a long ways off from being able to use the entire heart. An abundance of controversy of course surrounds the issue. https://www.cmaj.ca/content/180/13/1290 I never heard of that before. Pigs are a known quantity with a fully mapped genome and loads of research groups around the world tinkering with them. Edited January 15, 2022 by SpankyMcFarland Quote Link to comment Share on other sites More sharing options...
eyeball Posted January 16, 2022 Report Share Posted January 16, 2022 1 hour ago, SpankyMcFarland said: I never heard of that before. Pigs are a known quantity with a fully mapped genome and loads of research groups around the world tinkering with them. I think one of the reasons seal heart valves were proposed was that were deemed to be pretty hardy as a result of having evolved in a cold environment. Apparently they're also the right size. I think the biggest market would likely be for people that aren't interested in utilizing pigs. Quote Link to comment Share on other sites More sharing options...
SpankyMcFarland Posted January 16, 2022 Author Report Share Posted January 16, 2022 OK, I can see seal valves being durable given the depths they dive to. They’re basically acellular aren’t they? In any case there’s much less of a rejection problem with them than with full organs. Quote Link to comment Share on other sites More sharing options...
SpankyMcFarland Posted January 16, 2022 Author Report Share Posted January 16, 2022 I was surprised to learn that this not the first time a surgeon has attempted such an operation. In 1997 an Indian surgeon had a go without the gene modification etc. etc. The patient died and he was jailed. https://timesofindia.indiatimes.com/home/science/in-1997-this-indian-doctor-tried-pig-heart-transplant-was-jailed/articleshow/67111349.cms Quote Link to comment Share on other sites More sharing options...
SpankyMcFarland Posted January 17, 2022 Author Report Share Posted January 17, 2022 Here’s a little more detail on what the four knocked out genes coded for: GalSafe pigs, or pigs that had undergone editing to knock out a gene that codes for Alpha-gal (a sugar molecule) were used. Alpha-gal can elicit a devastating immune response in humans. GalSafe pigs have been well studied, and are approved by the US Food and Drug Administration (FDA) for use in pharmacology. “Building on the GalSafe platform, two other carbohydrate antigens were eliminated by knockout of the CMAH and Beta-4-Gal genes of the pig. To maintain a human-sized organ, the growth hormone receptor gene was also knocked out,” a spokesperson for the University of Maryland School of Medicine told The Indian Express in an email. Click to expand... And the six added human genes: “Two human complement inhibitor genes (CD46 and DAF), two human anti-coagulant genes (EPCR and Thrombomodulin), and two human immune-modulating genes (CD47 and HO1) were inserted in a targeted fashion into the genome of the donor pig,” the spokesperson said. Explained: How surgeons gave a pig heart — and hope of life — to a human The patient, David Bennett (57), was deemed ineligible for a conventional heart transplant or an artificial heart by leading transplant centres after a review of his medical records. indianexpress.com Quote Link to comment Share on other sites More sharing options...
SpankyMcFarland Posted September 26, 2023 Author Report Share Posted September 26, 2023 (edited) On September 20, 2023, a second patient received a genetically altered pig heart transplant. Additional efforts were made this time to suppress rejection of the heart and screen for the virus that may have helped to kill the first patient. https://www.nytimes.com/2023/09/22/health/pig-heart-transplant-faucette.html?smid=nytcore-ios-share&referringSource=articleShare Some info on a drug used in this second case that should reduce the risk of rejection. https://www.globenewswire.com/news-release/2023/09/25/2748502/0/en/Eledon-Pharmaceuticals-Announces-Use-of-Tegoprubart-anti-CD40L-Antibody-in-Second-ever-Transplant-of-Genetically-Modified-Heart-from-a-Pig-to-a-Human.html Edited September 27, 2023 by SpankyMcFarland Quote Link to comment Share on other sites More sharing options...
herbie Posted September 26, 2023 Report Share Posted September 26, 2023 And if he makes it to 2028 Captain Pigheart could be President! 1 Quote Link to comment Share on other sites More sharing options...
SpankyMcFarland Posted October 23, 2023 Author Report Share Posted October 23, 2023 Good news in our sea of gloom. Mr. Faucette is still alive one month after his transplant. He and his wife seem to have a great attitude to his perilous situation. So far there has been no sign of infection or rejection. https://www.cnn.com/2023/10/20/health/pig-heart-transplant-maryland-update/index.html#:~:text=medicines from shelves.-,One month after experimental pig heart transplant%2C doctors say they,signs of rejection or infection&text=Lawrence Faucette does physical therapy,receive experimental pig heart transplant. 1 Quote Link to comment Share on other sites More sharing options...
SpankyMcFarland Posted November 1, 2023 Author Report Share Posted November 1, 2023 (edited) Lawrence Faucette has just died: https://edition.cnn.com/lawrence-faucette-second-pig-heart-transplant-dies/index.html Edited November 1, 2023 by SpankyMcFarland Quote Link to comment Share on other sites More sharing options...
Perspektiv Posted January 10 Report Share Posted January 10 On 1/15/2022 at 3:28 PM, SpankyMcFarland said: There are also those may be put off specifically by a pig donor for religious reasons. This is what is concerning? Not that its a pig? Quote Link to comment Share on other sites More sharing options...
SpankyMcFarland Posted January 20 Author Report Share Posted January 20 On 1/10/2024 at 12:27 PM, Perspektiv said: This is what is concerning? Not that it’s a pig? I’d say those concerns are mixed together. There is a visceral fear of receiving an animal’s organ that is understandable. Quote Link to comment Share on other sites More sharing options...
SpankyMcFarland Posted March 22 Author Report Share Posted March 22 On March 16, Rick Slayman, a 62 year old man with terminal kidney failure and multiple other serious medical problems, received a pig kidney. The pig donor was genetically altered in a similar way to the pigs used in the two Maryland heart transplants above but was a different type of pig. Recently, a pig kidney transplanted into a brain-dead human patient survived for a month. So far, Mr. Slayman is doing well. https://www.cnn.com/2024/03/21/health/pig-kidney-transplant-living-person/index.html https://www.massgeneral.org/news/press-release/worlds-first-genetically-edited-pig-kidney-transplant-into-living-recipient Quote Link to comment Share on other sites More sharing options...
SpankyMcFarland Posted March 22 Author Report Share Posted March 22 Incredibly, the medical team is talking about discharging the patient ‘soon’, a very different situation from the cardiac recipients above. The pig breed used in the Maryland heart cases was a fairly standard size bigger than humans which had to be genetically modified to make it smaller whereas the kidney came from a ‘mini pig’. Quote While eGenesis also includes the six human transgenes in its pigs, “we only do three knockouts because we're working in what's called a Yucatan mini pig, so it's a smaller pig,” he said. “The Revivicor team is working in large white pigs, and they have to deal with the heart overgrowing the recipient. So to limit the size of the organ, they make this growth hormone receptor knockout. . . . We don't have to do that.” However, there is a particular potential risk with this type of pig: Quote Working with the Yucatan mini pig holds the advantage in terms of size, but these animals have a higher likelihood of the porcine retrovirus PERV-C, which could be dangerous if passed onto humans. “We go right at it and try to robustly inactivate retroviruses using CRISPR-Cas9,” while Revivicor hearts innately should be PERV-C-free, Curtis said. “Those are different philosophies of how to address the retrovirus transmission risk. We'll see which one is actually the best.” Quote https://www.tctmd.com/news/realistic-expectations-emerge-after-initial-excitement-over-xenotransplant Quote Link to comment Share on other sites More sharing options...
Aristides Posted March 23 Report Share Posted March 23 The first human heart transplant recipient only lived 18 days. My guess is this has a future 1 Quote Link to comment Share on other sites More sharing options...
SpankyMcFarland Posted March 23 Author Report Share Posted March 23 (edited) 2 hours ago, Aristides said: The first human heart transplant recipient only lived 18 days. My guess is this has a future For sure, especially with easier-to-transplant organs like kidney. I believe a pig kidney has already survived in a monkey for two years. https://www.cbc.ca/news/health/pig-organs-1.6993364 One alternative to an animal donor, creating a kidney from the recipient’s own stem cells, seems like a long way from becoming a reality at the moment. There are certainly many thousands of patients whose lives would be prolonged and immeasurably improved if this form of animal-to-human transplantation works out. With the current epidemic of obesity in the young we are facing a massive increase in diabetic kidney failure. What a coup for South Africa that first transplant was! Edited March 23 by SpankyMcFarland Quote Link to comment Share on other sites More sharing options...
SpankyMcFarland Posted April 4 Author Report Share Posted April 4 At long last I have some good news to report on this thread. Richard Slayman, the man who received a pig kidney last month, was discharged from hospital today. Quote “I want to thank everyone at Massachusetts General Hospital who cared for me before and after my historic transplant, especially Dr. Williams, Dr. Riella, Dr. Kawai, and the countless nurses who looked after me every day of my stay,” Slayman said. Quote Slayman is a system manager at the Department of Transportation, who has worked throughout his battle with diabetes and kidney failure. Quote “I’m excited to resume spending time with my family, friends, and loved ones free from the burden of dialysis that has affected my quality of life for many years,” Slayman said. “Lastly, I want to thank anyone who has seen my story and sent well-wishes, especially patients waiting for a kidney transplant,” he added. “Today marks a new beginning not just for me, but for them, as well. My recovery is progressing smoothly and I ask for privacy at this time.” https://www.bostonherald.com/2024/04/03/the-massachusetts-man-who-received-a-pig-kidney-transplant-discharged-from-mgh-one-of-the-happiest-moments-of-my-life/ Of course it is early days yet. Let’s hope this brave man does well. Quote Link to comment Share on other sites More sharing options...
SpankyMcFarland Posted April 9 Author Report Share Posted April 9 Oh no, something I didn’t hear of until today. While in hospital, the patient had an episode of acute cellular rejection. Apparently it has been treated. Quote …on the eighth day, the kidney began showing signs that it was struggling. Doctors performed a biopsy and discovered that white blood cells had started to infiltrate the transplanted organ, causing swelling and inflammation — classic signs of the most common type of acute graft rejection, known as cellular rejection. It’s something transplant nephrologists like Riella see in about 20% of patients receiving kidneys from human donors, and is treatable using high doses of steroids and a drug that depletes the body’s ranks of T cells. Slayman’s doctors started him on these drugs, and after a tense three days, his body began to respond to treatment and his new kidney’s function improved. They also upped the immunosuppressant regimen he will be on for the foreseeable future as a precautionary measure against future rejection episodes. They had to advise him he couldn’t go back to work for at least two months. You wouldn’t have to tell me that. https://www.statnews.com/2024/04/08/xenotransplantation-pig-kidney-rejection-richard-slayman/ Quote Link to comment Share on other sites More sharing options...
SpankyMcFarland Posted April 11 Author Report Share Posted April 11 China just made a big leap forward in the field of pig kidney to human transplantation. BTW they transplanted a pig liver too. https://www.wionews.com/science/doctors-in-china-successfully-transplant-pig-kidney-into-brain-dead-human-patient-709688 Quote Link to comment Share on other sites More sharing options...
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