Genetically modified pig kidneys implant in brain-dead patients

A surgeon at the University of Alabama at Birmingham reported on Thursday that he was the first to successfully transplant a kidney from a genetically modified pig into the abdomen of a 57-year-old brain-dead man.

This announcement was the latest in a series of notable feats in organ transplantation. Earlier this month, a surgeon at the University of Maryland transplanted a transgenic pig heart into a 57-year-old patient with heart failure. The patient is still alive and being observed.

In September, a NYU Langone Health surgeon attached a recombinant pig kidney to a ventilated brain-dead person. The kidneys remained outside the body, but they worked normally for 54 hours, and urine and creatinine became waste products.

UAB surgery Reported The American Journal of Transplantation first published a peer-reviewed medical journal on organ transplants from pigs to humans.

According to the surgical team, the pig’s kidneys functioned after about 23 minutes and began to produce urine, one kidney producing more urine than the other, but continued for three days.

The patient’s own kidney was removed and there were no signs of rejection of the pig’s organs.

Dr. James Locke, Principal Surgeon, said that this procedure strictly follows all steps of normal human-to-human transplant surgery, addresses important safety questions, and is small-scale for living patients. He said he laid the foundation for clinical trials. She wanted to start by the end of the year.

Many of the previous operations were unique experiments, not part of an ongoing trial.

“Our goal is to move this area forward to help patients, not just one-off,” said Dr. Locke, director of the UAB’s incompatible kidney transplant program. “What a wonderful day I can step into the clinic and find out that everyone waiting to see me has kidneys.”

Alabama has one of the highest incidences of chronic kidney disease in the country, with 2,348 cases per million inhabitants. Kidney disease, often the result of diabetes and high blood pressure, is most common in older people, but it affects disproportionately in people of color, women, and poorly educated and low-income people.

In Alabama, kidney disease rates are abnormally high in adults aged 45 to 64 years. Patients with kidney disease who have not received a transplant from a compatible donor should receive dialysis treatment three times a week for each hour.

“We believe that renal failure is intractable, serious and influential, and we need a radical solution,” said Dr. Rock. She hopes to be able to provide a patient with a porcine kidney transplant within five years, as long as she “achieves all milestones and is free of setbacks.”

In the paper, she and the other authors thanked James Parsons, a family member of a brain-dead individual, for agreeing to the study and to Parsons, a registered organ donor from Huntsville. He said he would name this type of study afterwards. Injury during a motorcycle race in September.

Relatives described Parsons as a united person who loves to help people as much as possible. The family immediately agreed to the study.

“He will be excited to benefit a lot of people,” Parsons’ sister Amy Parsons Bourne said in an interview. “Too many people need kidneys.”

Over 500,000 Americans have end-stage renal disease and are dependent on dialysis. Transplantation is the best treatment for renal failure, but the rapid shortage of donor organs makes the option out of reach for the majority of patients.

As of last summer, more than 90,000 people were on the kidney waiting list. The waiting period can be long. Less than 25,000 kidney transplants are performed each year in the United States, killing more than 12 people on the waiting list every day.

Researchers have long sought to grow pig organs suitable for transplantation into humans. In recent years, new technologies such as cloning and genetic engineering have brought that vision closer to reality.

Xenotransplantation, a method of transplanting animal organs into humans, has been well underway and has begun for decades. However, over the past few months, surgeons in this area have reported a series of new achievements.

At NYU Langone in September, surgeons experimented with kidneys removed from pigs that were genetically modified so that the tissue did not cause aggressive human rejection. The kidneys were attached to the patient’s thighs and appeared to function as kidneys, producing urine and creatinine (waste) for 54 hours.

But the most amazing such procedure occurred in early January at the University of Maryland Medical Center. The patient, David Bennett Sr., was given a transgenic porcine heart, exhausting all other treatment options.

He was separated from the heart-lung machine on January 11. He is fine and has not rejected animal organs, said Dr. Muhammad Mohiudin, director of science at the University of Maryland Cardiac Xenograft Program.

“Twelve days have passed and he is making progress. The heart is beating like a new heart,” said Dr. Mohiudin. “It’s like having a BMW engine in a car from the 1960s.”

The heart Bennett received was taken from a pig whose genome was altered 10 times, including the removal of four genes to prevent rejection and the continued growth of organs.

In addition, six human genes have been inserted into the donor pig’s genome, making the organ more tolerant of the human immune system.

Pigs were provided by Reviver, a subsidiary of United Therapeutics Corporation. Reviver is the lead author of a paper explaining kidney transplantation, helping to fund the study, and UAB, and Dr. Rock and two other research authors. The other four authors of the paper are Revivicor employees.

According to experts, the fact that these pig organs have not been rejected is a big achievement.

“The greatest fear in the xenograft community was hyperacute immune rejection. When placed in a new organ, the body immediately rejects it,” said Dr. Mohiudin.

Dr. Robert Montgomery, director of the NYU Langone Transplant Institute, said he welcomed the opportunity to learn more about xenotransplantation through work done at other centers.

“I’m particularly interested in what new information we can learn about kidney function, given the significant differences in the genetic modification and transplantation processes from our research,” he said. rice field.

He and other surgeons at NYU Langone said he had attached another pig’s kidney to a brain-dead patient on November 22nd.

Dr. Locke said care was taken to ensure that kidney surgery at UAB closely reflected standard allogeneic transplants, human-to-human transplants.

Pig organs were removed in a sterile surgical facility that meets the certification standards of human hospitals. To confirm that brain-dead people do not yet have antibodies to the organs of the pig that cause rejection, a conformity test, which is the standard prior to transplant surgery, was developed.

Surgeons also removed Parsons’ kidneys to confirm that Parsons’ urine was actually made by pig kidneys, and only standard immunosuppressive drugs already widely used in allogeneic transplants. I administered it.

“This is part of a larger program to ensure that we can transfer this to living people in a responsible manner,” said UAB’s Director of Clinical Translational Research at the Transplantation Institute. One Dr. Pollet said.

“We wanted to take everything out for a human test drive, so when we provide it to the patient, we do everything we can to see the patient and see what this looks like. You can say that you did a job. “