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Johns Hopkins surgeons get $21.4 million to study pig-to-human organ transplants

April 5, 2023

Angela Roberts | (TNS) The Baltimore Sun

BALTIMORE — Two Johns Hopkins Medicine surgeons will receive $21.4 million over the next two years to advance research needed to successfully transplant living cells, tissues and organs from animals to humans.

The scientists, Dr. Kazuhiko Yamada and Dr. Andrew Cameron, will receive the funding under two research agreements with the United Therapeutics Corp., a biotechnology company that focuses on projects meant to expand the availability of transplantable organs, Johns Hopkins Medicine said last week in a news release.

Over the next two years, Yamada and Cameron plan to advance the use of genetically modified pigs in human organ transplants, improving techniques already used in the approach to reduce the risk of organ rejection and failure and to increase the likelihood of a patient’s long-term survival.

The funding will help Yamada and Cameron complete the necessary studies in animals requested by the U.S. Food and Drug Administration before the first clinical trials of genetically modified pig kidney transplants in humans can begin, the researchers said in the release.

“Then, hopefully, we can finally realize that promise,” Yamada, a surgery professor at the Johns Hopkins University School of Medicine, said in the release.

Human clinical trials could lead to xenotransplantation — the transplantation of living cells, tissues and organs from one species to another — becoming a way of alleviating the nation’s organ transplant shortage, said Cameron, surgeon-in-chief and director of the Hopkins medical school’s department of surgery.

The number of usable organs for transplantation remains extremely low in the U.S. According to the federal Health Resources & Services Administration’s organdonor.gov, 17 people die every day because they cannot get a transplantable organ.

Last year, there were about 96,000 people on waiting lists for a kidney, but only about 25,500 transplants were performed, according to the agency’s Organ Transplantation & Donation Network. End-stage kidney disease, which results in kidney failure and death without treatment, can only be remedied with dialysis or a kidney transplant from a deceased or living donor, the release read.

For decades, researchers worldwide have investigated the potential of using pig organs — primarily hearts and kidneys — for xenotransplantation in humans because of similarities between the species in how their organs work. Though the FDA has not yet approved these kinds of transplants for clinical use, the agency has permitted “compassionate use” exceptions on rare occasions, according to the release.

Yamada, who was recruited in August to lead Johns Hopkins Medicine’s xenotransplantation research program, performed the first pig-to-primate kidney transplant in 2003 using genetically modified pig kidneys.

Doctors at the University of Maryland School of Medicine and the University of Maryland Medical Center transplanted a genetically modified pig heart into man in January 2022 to save his life. The man died two months later of heart failure. However, in the weeks after the transplant, the man who had been bedridden was able to get out of bed, begin rehabilitation and spend time with his family.

“It was either die or do this transplant. I want to live,” the man said in a statement before the operation. “I know it’s a shot in the dark, but it’s my last choice.”

To boost the chances of a successful pig-to-human organ transfer, researchers modify swine so that they don’t have the gene that produces alpha-gal sugar — a compound on cell surfaces that stimulates the immune system and is believed to be a trigger of transplant rejections in humans.

Under the new research agreements, Yamada and Cameron will study this technique — called a gene “knockout” — as well as “knocking in,” or adding, human genes to the donated pig organ to make it seem more human.

The researchers also will study an approach meant to teach the human immune system to recognize the donated pig organ as its own ― transplanting a pig kidney concurrently with thymus tissue from the same animal. The thymus gland is a small organ that lies in the upper chest, under the breastbone, that makes white blood cells, which protect the body against infections.

“By transplanting pig thymus tissue along with the donor kidney, the immune response of the recipient is reduced, prolonging the viability of the organ, and with less need for medical immunosuppression,” said Yamada, who pioneered the transplant approach.

Orange County Register

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Johns Hopkins surgeons get $21.4 million to study pig-to-human organ transplants

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