Medical milestone: Monkey lives for 758 days with pig kidney
Xenotransplantation is one possible approach to tackle the severe shortage of human organs.
It entails transplanting organs or tissues from one species, generally pigs, into another, such as humans.
However, before xenotransplantation can be considered a feasible alternative for human patients, scientists have been performing considerable research and studies on animal models to examine the procedure’s safety and efficacy.
A significant breakthrough in the field of xenotransplantation has been achieved through a recent study. This study demonstrated the more prolonged survival of animal recipients who got genetically engineered pig kidneys, with one monkey living for over two years (758 days).
This “extraordinary milestone” was achieved by a team of researchers from the Harvard Medical School and the US biotech company eGenesis. The latter’s goal is to develop human-compatible organs to treat organ failure.
“This is a major step forward for the field of transplantation. One of the biggest hurdles has been the long-term survival of the genetically engineered organ in the NHP recipient [non-human-primate], said Tatsuo Kawai, M.D., Ph.D., Professor of Surgery at Harvard Medical School, in the company’s press statement.
Genetically modified pig kidney
Scientists have been researching the viability of animal-to-human organ transplants for decades. The primary goal is to guarantee that animal organs operate efficiently and safely when transplanted into human patients, all while avoiding immune system rejection.
However, it has been proven to be incredibly daunting for many years. But, the advent of the remarkable gene-editing tool CRISPR-Cas9 has brought some promising solutions.
This technology allows for the deliberate modifications of a chosen animal’s genome, permitting the elimination of harmful genes, including removing viruses genes inherent in the animals.
The technique also enables the addition of some pivotal genes to make the organ compatible with the recipient’s body.
The ultimate goal is to trick the recipient’s immune system into recognizing the foreign organ as one of its own, allowing it to operate properly once inside the body.
Pigs are frequently employed in xenotransplantation studies because their organs are anatomically comparable to humans in terms of organ size and physiological metabolism.
Human and other primates’ immune systems are known to naturally respond to three specific molecules present on the surfaces of pig cells. This raises the likelihood of unaltered pig organs being rejected right away.
To address this issue, the researchers used genome-editing techniques to disable these specific genes in this study.
The company seeks FDA nod
For this trial, a total of 69 genes were edited — marking the most extensive gene editing conducted in animals for xenotransplantation.
Some of these changes involved the inclusion of at least seven human transgenes that serve to maintain the transplanted organ healthy and avoid unwanted blood clotting.
69 distinct genetic modifications were performed on Yucatan miniature pigs, and the recipients were crab-eating macaques.
The experiment results showed that kidneys incorporated with seven human genes allowed monkeys to live for at least 176 days.
In the case of kidneys modified with seven human genes and coupled with immune system suppression therapy, one of the recipient monkeys has lived for over two years or roughly 758 days. The monkey is still being watched over.
This new development brings researchers one step closer to potential human applications. Following this study, the company actively seeks approval from the US Food and Drug Administration to begin a human clinical study.
“This dataset will support the advancement of the company’s lead candidate for kidney transplant, EGEN-2784, toward clinical development. These results represent the largest and most comprehensive preclinical dataset published in the field to date. Recipient survival in the preclinical setting has historically been measured in weeks or months,” noted the release.
Reportedly, to date, two individuals have undergone pig heart transplants.
Unfortunately, David Bennett, the first recipient, died two months following the procedure in 2022. The second person, 58-year-old Lawrence Faucette, underwent a pig heart transplant in September and is recovering.
The company also aims to assess the effectiveness and safety of other genetically modified organs, such as the heart and liver, for xenotransplant.
Because of the shortage of organ donors, research in this field is critical. In the United States alone, over 100,000 individuals need an organ transplant, and tragically, approximately 17 of them lose their lives each day while waiting for a suitable donor.
The results were reported in the journal Nature.
Source: https://interestingengineering.com