世界で初めてブタ腎臓の移植を受けた患者が退院
臓器移植のドナー不足を解消する突破口となる可能性
遺伝子を編集したブタからの臓器移植は、過去2回失敗しているが、Slayman氏の新しい腎臓は、尿の生成および血液中の老廃物の除去ができていると、米マサチューセッツ総合病院（MGH）の医師らは語っている。
このブタの腎臓は、米eGenesis社から提供されたものである。同社は、ブタの臓器をヒトに移植可能にするための、遺伝子編集の実験を行ってきた会社である。同社は2023年に「Nature」に、同社のブタの腎臓の1つを移植されたサルが、2年以上生存していることを報告した。
研究者らによると、Slayman氏が移植された腎臓は、有害なブタの遺伝子を除去し、有用なヒトの遺伝子を追加する、69の遺伝子編集が施されている。また、ドナーとなったブタのレトロウイルスが、ヒトへの感染の危険性を排除するために不活化された。
米MGHの腎臓科の副部長で、Slayman氏の主治医であるWinfred Williams氏曰く、この遺伝子編集されたブタの腎臓は、「極端なドナー臓器不足やその他の組織的障壁のために、民族的マイノリティである患者は腎臓移植の平等な機会が得られないという、われわれの分野における難問の1つを解決する突破口になり得る」と述べている。
医師らによるとSlayman氏の手術は2月に米食品医薬品局（FDA）から、未承認の治療へのアクセスを許可する「compassionate use」を与えられ、実施された。
Slayman氏は拒絶反応を抑制するため、2種類の新たな免疫抑制剤（エレドン・ファーマシューティカルズ社が提供するtegoprubartおよびアレクシオン・ファーマ社が提供するラブリズマブ）を点滴投与された。
Photo Credit: 米マサチューセッツ総合病院/Michelle Rose氏
First Pig Kidney Transplant Patient Discharged From Hospital
THURSDAY, April 4, 2024 (HealthDay News) -- Rick Slayman, the first person to receive a kidney transplant from a genetically modified pig, headed home Wednesday after faring so well that he was released from the hospital just two weeks after his groundbreaking surgery.
“This moment -- leaving the hospital today with one of the cleanest bills of health I’ve had in a long time -- is one I wished would come for many years. Now, it’s a reality and one of the happiest moments of my life," Slayman said in a statement.
"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," the 62-year-old added. "Lastly, I want to thank anyone who has seen my story and sent well-wishes, especially patients waiting for a kidney transplant. Today marks a new beginning not just for me, but for them, as well.”
Experts agreed.
“Though much work remains to be done, I think the potential of this to benefit a large number of patients will be realized, and that was a question mark hovering over the field,” Dr. David Klassen, chief medical officer for the United Network for Organ Sharing (UNOS), told the New York Times.
While two previous organ transplants from genetically modified pigs had failed, Slayman's new kidney is producing urine and removing waste products from the blood, his doctors at Massachusetts General Hospital (MGH) said.
After the transplant was completed, Dr. Winfred Williams, associate chief of the nephrology division at MGH and Slayman's primary kidney doctor, hailed his patient's “courageousness in becoming a trailblazer in the field of transplantation.”
The pig kidney came from eGenesis, a Cambridge, Mass., company that has been experimenting with genetic alterations to make pig organs transplantable to humans.
Last year, eGenesis reported in the journal Nature that a monkey had been living with one of its transplanted pig kidneys for two years.
The kidney Slayman received had 69 genetic edits that removed harmful pig genes and added helpful human genes, researchers said. Scientists also inactivated retroviruses in the pig donor to eliminate any risk of infection in humans.
Slayman is Black, and Black patients tend to suffer high rates of end-stage kidney disease, the Times reported.
These genetically altered pig kidneys represent a “potential breakthrough in solving one of the more intractable problems in our field, that being unequal access for ethnic minority patients to the opportunity for kidney transplants due to the extreme donor organ shortage and other system-based barriers,” Williams said.
Slayman has been living with type 2 diabetes and high blood pressure for many years, doctors said. He received a kidney transplant from a human donor in December 2018, but the organ began to fail after five years and he resumed dialysis in May 2023.
He’s since been in and out of the hospital regularly, due to complications stemming from his dialysis, doctors said.
More than 100,000 people in the United States are awaiting an organ for transplant, according to the UNOS. About 17 people die each day for want of a donor organ.
Kidneys are the most common organs needed for transplant, doctors said. End-stage kidney disease rates are expected to increase from 29% to 68% in the United States by 2030.
“At MGH alone, there are over 1,400 patients on the waiting list for a kidney transplant. Some of these patients will unfortunately die or get too sick to be transplanted due to the long waiting time on dialysis. I am firmly convinced that xenotransplantation represents a promising solution to the organ shortage crisis,” said Dr. Leonardo Riella, MGH medical director for kidney transplantation.
Slayman's procedure was performed under a compassionate use waiver granted by the U.S. Food and Drug Administration in February, doctors said.
To help Slayman avoid rejection, he also received an infusion of two new immunosuppressant drugs -- tegoprubart, provided by Eledon Pharmaceuticals Inc., and ravulizumab, provided by Alexion Pharmaceuticals Inc.
More information
The U.S. National Institutes of Health has more about kidney transplantation.
SOURCE: Massachusetts General Hospital, news releases, April 3, 2024, March 21, 2024; New York Times
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IMAGE: Image: Mass General Hospital/Michelle Rose
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