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2024.03.21 

ブタ腎臓のヒトへの移植、世界初の成功

末期腎不全の患者に遺伝子編集されたブタ腎臓を移植

末期腎不全(ESKD)患者に対し、遺伝子編集されたブタ腎臓を移植することに成功したと、米マサチューセッツ総合病院(MGH)の移植センターの医師らが報告した。移植用のブタ腎臓は、拒絶反応や疾患のリスクを下げるために遺伝子編集されたものであり、サルや脳死ドナーへの移植例はあったが、実際の患者への移植は世界初という。

3月16日、Rick Slayman氏(62歳)は4時間にわたる手術を受け、遺伝子編集されたブタ腎臓を移植された。米マサチューセッツ州に居住する同氏は、順調に回復しており、間もなく退院できる見込みだという。

Slayman氏は、MGHの医師らから移植を提案され、その長所と短所を注意深く説明された後、移植に同意し、「自分を助けるだけでなく、生き残るために移植を必要とする何千人もの人々に希望を与える方法だと考えた」と、MGHのニュースリリースで語っている。

今回のブタ腎臓は、同州に所在するeGenesis社から提供されたものである。同社は、ブタ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進めてきた会社であり、昨年、1つのブタ腎臓を移植されたサルが2年間生存していることを「Nature」に報告している。

Slayman氏が移植を受けた腎臓は、有害なブタの遺伝子を除去し、有益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たという。また、ヒトへの感染リスクを排除するため、ドナーであるブタのレトロウイルスの不活化も実施している。

MGHの腎臓内科副部長で、患者の主治医であるWinfred Williams氏は、Slayman氏の「移植分野の先駆者となる勇気」を称えた。同氏はこの遺伝子編集されたブタの腎臓について、「われわれの分野の最も難しい問題の1つは、極めて深刻なドナー臓器不足とその他のシステム上の障壁のために、マイノリティ患者が腎臓移植を受ける機会には格差が存在しているということだ。その解決のための画期的な突破口になる可能性がある」と述べている。

Slayman氏は長年、2型糖尿病と高血圧を患っており、2018年12月にヒトのドナーから腎臓移植を受けたが、5年後に臓器が機能不全に至り、2023年5月に透析を再開した。それ以来、彼は透析に起因する合併症のため、定期的に入退院を繰り返していたという。

今回の手術は、2月に米食品医薬品局(FDA)が承認した人道的使用許可(compassionate use waiver)の下で施行された。Slayman氏は拒絶反応を抑制するため、2種類の新しい免疫抑制薬(Eledon Pharmaceuticals社が提供するtegoprubart、Alexion Pharmaceuticals社が提供するravulizumab)の点滴を受けている。

kidney transplantation

SOURCE: Massachusetts General Hospital, news release, March 21, 2024


Image: Massachusetts General Hospital

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2024.03.21 

Surgeons Implant Pig Kidney Into First Living Human Patient

THURSDAY, March 21, 2024 (HealthDay news) -- For the first time ever, doctors have transplanted a genetically edited pig kidney into a human suffering from advanced kidney failure.


Such pig kidneys, altered to lower the risk of rejection and disease, have been successfully placed into monkeys and brain-dead human donor bodies.


But Rick Slayman, 62, is the first living patient to receive a gene-edited pig kidney, in an operation last weekend that took four hours, according to his doctors at Massachusetts General Hospital (MGH) in Boston.


The Weymouth, Mass., resident is recovering well and is expected to be discharged soon, his doctors said.


Slayman said he agreed to the transplant after MGH doctors suggested it, “carefully explaining the pros and cons of this procedure.”


“I saw it not only as a way to help me, but a way to provide hope for the thousands of people who need a transplant to survive,” Slayman said in a hospital news release.


Dr. Winfred Williams, associate chief of the nephrology division at MGH and the patient’s primary kidney doctor, hailed Slayman’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 New York 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 United Network for Organ Sharing. 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.


Last weekend’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 release, March 21, 2024


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IMAGE: Image: Massachusetts General Hospital

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