文章為轉(zhuǎn)載，原始來(lái)源：https://nyulangone.org/news/pig-kidney-xenotransplantation-performing-optimally-after-32-days-human-body

做了機(jī)翻，在文末。

NEW YORK, NY, AUGUST 16, 2023 — Surgeons at NYU Langone Health have transplanted a genetically engineered pig kidney that continues to function well after 32 days in a man declared dead by neurologic criteria and maintained with a beating heart on ventilator support. This represents the longest period that a gene-edited pig kidney has functioned in a human, and the latest step toward the advent of an alternate, sustainable supply of organs for transplant.

Multimedia Materials Available Multimedia materials, including photos and a B-roll package, are available for download.

About the Procedure The procedure, performed on July 14, 2023, and led by Robert Montgomery, MD, DPhil, the H. Leon Pachter, MD Professor of Surgery, chair of the Department of Surgery, and director of the NYU Langone Transplant Institute, was the fifth xenotransplant performed at NYU Langone. Observation is ongoing and the study will continue through mid-September 2023.

“This work demonstrates a pig kidney—with only one genetic modification and without experimental medications or devices—can replace the function of a human kidney for at least 32 days without being rejected,” said Dr. Montgomery, who had previously performed the world’s first genetically modified pig kidney transplant into a human decedent on September 25, 2021, followed by a second similar procedure on November 22, 2021. Surgeons with the Transplant Institute performed two genetically engineered pig heart transplants in summer 2022.

Removing Troublesome Gene Again Shows Promise

The first hurdle to overcome in xenotransplants is preventing so-called hyperacute rejection, which typically occurs just minutes after an animal organ is connected to the human circulatory system. By “knocking out” the gene that encodes the biomolecule known as alpha-gal—which has been identified as responsible for a rapid antibody-mediated rejection of pig organs by humans—immediate rejection has been avoided in all five xenotransplants at NYU Langone. Additionally, the pig’s thymus gland, which is responsible for educating the immune system, was embedded underneath the outer layer of the kidney to stave off novel, delayed immune responses. The combination of modifications has been shown to prevent rejection of the organ while preserving kidney function.

To ensure the body’s kidney function was sustained solely by the pig kidney, both of the transplant recipient’s native kidneys were surgically removed. One pig kidney was then transplanted and started producing urine immediately without any signs of hyperacute rejection. During the observation phase, intensive care clinical staff maintained the decedent on support while the pig kidney’s performance was monitored and sampled with weekly biopsies. Levels of creatinine, a bodily waste product found in the blood and an indicator of kidney function, were in the optimal range during the length of the study, and there was no evidence on biopsy of rejection.

The surgery was the latest in a larger study approved by a specific research ethics oversight board at NYU Langone and was performed after consultation with the New York State Department of Health. This important research, which study leaders say could save many lives in the future, was made possible by the family of a 57-year-old male who elected to donate his body after a brain death declaration and a circumstance in which his organs or tissues were not suitable for transplant.

LiveOnNY, the nonprofit organization that facilitates organ and tissue donation in the greater New York City area, was a critical partner in the effort to inform, support, and collaborate throughout the authorization process with the donor family.

A Big Leap Toward a New Organ Source

In the United States, there are more than 103,000 people on the waiting list for transplant, with nearly 88,000 of those waiting for a kidney, according to recent federal Organ Procurement and Transplantation Network (OPTN) data. In 2022, about 26,000 people received a kidney transplant. Meanwhile, nearly 808,000 people in the U.S. have end-stage renal disease.

“There are simply not enough organs available for everyone who needs one,” said Dr. Montgomery, who received a hepatitis C–positive heart transplant himself in 2018. “Too many people are dying because of the lack of available organs, and I strongly believe xenotransplantation is a viable way to change that.”

The kidney and thymus gland used in this procedure were procured from a GalSafeTM pig, an animal engineered by Revivicor, Inc., a subsidiary of United Therapeutics Corporation. In December 2020, the U.S. Food and Drug Administration (FDA) approved the GalSafe pig as a potential source for human therapeutics as well as a food source for people with alpha-gal syndrome, a meat allergy caused by a tick bite.

Less May Be More in Kidney Xenotransplants

While previous genetically engineered pig organ transplants have incorporated up to 10 genetic modifications, this latest study shows that a single-gene knockout pig kidney can still perform optimally for at least 32 days without rejection.

“We’ve now gathered more evidence to show that, at least in kidneys, just eliminating the gene that triggers a hyperacute rejection may be enough along with clinically approved immunosuppressive drugs to successfully manage the transplant in a human for optimal performance—potentially in the long-term,” said Dr. Montgomery.

The NYU Langone team used standard transplant immunosuppression medications combined with enhanced screening of porcine cytomegalovirus (pCMV) in the donor pig to ensure safety. Recent studies have shown pCMV may affect organ performance and potentially trigger organ failure. No pCMV was detected after 32 days, and close surveillance of porcine endogenous retrovirus (PERV), along with six other viruses of interest, was performed.

Next Steps

Monitoring of the pig kidney recipient will continue for another month with permission from the family, ethics committee approval, and continued support from United Therapeutics. The additional data from the next several weeks will be analyzed further to develop a deeper understanding of this unique medical advance.

“We think using a pig already deemed safe by the FDA in combination with what we have found in our xenotransplantation research so far, gets us closer to the clinical trial phase,” said Dr. Montgomery. “We know this has the potential to save thousands of lives, but we want to ensure the utmost safety and care as we move forward.”

GalSafe is a trademark of Revivicor, Inc.

Media Inquiries

Colin DeVries Phone: 212-404-3588 colin.devries@nyulangone.org

紐約州紐約，2023 年 8 月 16 日 — 紐約大學(xué)朗格尼健康中心的外科醫(yī)生移植了一種基因工程豬腎，該腎在 32 天后繼續(xù)運(yùn)作良好，該腎在一名根據(jù)神經(jīng)系統(tǒng)標(biāo)準(zhǔn)宣佈死亡並在呼吸機(jī)支援下維持心臟跳動(dòng)的男性身上。這代表了基因編輯豬腎臟在人類中發(fā)揮作用的最長(zhǎng)時(shí)間，也是朝著替代的、可持續(xù)的移植器官供應(yīng)的出現(xiàn)邁出的最新一步。

提供多媒體材料 多媒體材料，包括照片和B-roll包，可供下載。

關(guān)於該程式 該程式於 2023 年 7 月 14 日進(jìn)行，由羅伯特·蒙哥馬利醫(yī)學(xué)博士、DPhil、H. Leon Pachter、醫(yī)學(xué)博士外科教授、外科系主任和紐約大學(xué)朗格尼移植研究所所長(zhǎng)領(lǐng)導(dǎo)，是紐約大學(xué)朗格尼分校進(jìn)行的第五次異種移植。觀察正在進(jìn)行中，研究將持續(xù)到 2023 年 9 月中旬。

蒙哥馬利博士說(shuō)：“這項(xiàng)工作表明，豬腎——只有一種基因改造，沒(méi)有實(shí)驗(yàn)性藥物或設(shè)備——可以替代人類腎臟的功能至少 32 天而不會(huì)被拒絕，” 蒙哥馬利博士說(shuō)，他之前曾在 2021 年 9 月 25 日對(duì)人類死者進(jìn)行了世界上第一例轉(zhuǎn)基因豬腎移植， 隨後於 2021 年 11 月 22 日進(jìn)行了第二次類似的程式。移植研究所的外科醫(yī)生在 2022 年夏天進(jìn)行了兩次基因工程豬心臟移植手術(shù)。

去除麻煩基因再次顯示出希望

異種移植中要克服的第一個(gè)障礙是防止所謂的超急性排斥反應(yīng)，這通常發(fā)生在動(dòng)物器官連接到人體循環(huán)系統(tǒng)幾分鐘後。通過(guò)「敲除」編碼稱為α-gal的生物分子的基因 - 已被確定為人類對(duì)豬器官的快速抗體介導(dǎo)排斥的原因 - 在所有五種異種中都避免了立即排斥反應(yīng)紐約大學(xué)朗格尼分校的植物。此外，豬的胸腺，負(fù)責(zé)教育免疫系統(tǒng)，嵌入在腎臟的外層下，以避免新的，延遲的免疫反應(yīng)。修改的組合已被證明可以防止器官排斥，同時(shí)保留腎功能。

為了確保身體的腎功能僅由豬腎臟維持，移植受者的兩個(gè)自體腎臟都被手術(shù)切除。然後移植一頭豬腎並立即開(kāi)始產(chǎn)生尿液，沒(méi)有任何超急性排斥反應(yīng)的跡象。在觀察階段，重癥監(jiān)護(hù)臨床工作人員維持死者的支援，同時(shí)監(jiān)測(cè)豬腎的性能並通過(guò)每周活檢進(jìn)行採(cǎi)樣。肌酐（一種在血液中發(fā)現(xiàn)的身體廢物和腎功能指標(biāo)）的水準(zhǔn)在研究期間處?kù)蹲罴压?fàn)圍內(nèi)，並且沒(méi)有關(guān)於排斥反應(yīng)活檢的證據(jù)。

該手術(shù)是紐約大學(xué)朗格尼分校特定研究倫理監(jiān)督委員會(huì)批準(zhǔn)的一項(xiàng)大型研究中的最新一項(xiàng)，是在與紐約州衛(wèi)生部協(xié)商後進(jìn)行的。研究負(fù)責(zé)人表示，這項(xiàng)重要的研究可以在未來(lái)挽救許多生命，這是由一名57歲男性的家人實(shí)現(xiàn)的，他在宣佈腦死亡以及他的器官或組織不適合移植的情況下選擇捐贈(zèng)他的身體。

LiveOnNY 是一家促進(jìn)大紐約市地區(qū)器官和組織捐贈(zèng)的非營(yíng)利組織，是在整個(gè)授權(quán)過(guò)程中與捐贈(zèng)者家庭進(jìn)行通知、支援和合作的重要合作夥伴。

向新器官來(lái)源邁出一大步

在美國(guó)，有超過(guò)103，000人在等待移植的名單上，其中近88，000人等待腎臟，根據(jù)最近的聯(lián)邦器官採(cǎi)購(gòu)和移植網(wǎng)路（OPTN）da啪啪2022年，約有26，000人接受了腎移植手術(shù)。與此同時(shí)，美國(guó)有近808，000人患有終末期腎病。

“根本沒(méi)有足夠的器官供每個(gè)需要的人使用，”蒙哥馬利博士說(shuō)，他在2018年接受了丙型肝炎陽(yáng)性心臟移植手術(shù)?！坝伸度狈捎玫钠鞴?，太多人正在死亡，我堅(jiān)信異種移植是改變這種情況的可行方法。

該程式中使用的腎臟和胸腺是從GalSafeTM豬採(cǎi)購(gòu)的，GalSafeTM豬是由United Therapeutics Corporation的子公司Revivicor，Inc.設(shè)計(jì)的動(dòng)物。2020 年 12 月，美國(guó)食品和藥物管理局 （FDA） 批準(zhǔn) GalSafe 豬作為人類治療藥物的潛在來(lái)源，以及 α-半乳糖綜合征（一種由蜱蟲(chóng)叮咬引起的肉類過(guò)敏）患者的食物來(lái)源。

腎異種移植中少即是多

雖然以前的基因工程豬器官移植已經(jīng)包含了多達(dá)10種基因改造，但這項(xiàng)最新研究表明，單基因敲除豬腎仍然可以在至少32天內(nèi)保持最佳狀態(tài)而不會(huì)產(chǎn)生排斥反應(yīng)。

“我們現(xiàn)在收集了更多的證據(jù)表明，至少在腎臟中，僅僅消除引發(fā)超急性排斥反應(yīng)的基因可能就足以與臨床批準(zhǔn)的免疫抑製藥物一起成功地管理人類移植以獲得最佳性能 - 可能是長(zhǎng)期的，”蒙哥馬利博士說(shuō)。

NYU Langone團(tuán)隊(duì)使用標(biāo)準(zhǔn)移植免疫抑製藥物，並在供體豬中加強(qiáng)豬巨細(xì)胞病毒（pCMV）篩查，以確保安全性。最近的研究表明，pCMV可能會(huì)影響器官功能，並可能引發(fā)器官衰竭。32天后未檢出pCMV，並對(duì)豬內(nèi)源性逆轉(zhuǎn)錄病毒（PERV）以及其他六種感興趣的病毒進(jìn)行了密切監(jiān)測(cè)。

後續(xù)步驟

在家人的許可、倫理委員會(huì)的批準(zhǔn)以及聯(lián)合治療公司的持續(xù)支援下，對(duì)豬腎接受者的監(jiān)測(cè)將再持續(xù)一個(gè)月。未來(lái)幾周的其他數(shù)據(jù)將進(jìn)一步分析，以更深入地瞭解這一獨(dú)特的醫(yī)學(xué)進(jìn)步。

“我們認(rèn)為使用FDA已經(jīng)認(rèn)為安全的豬，結(jié)合我們迄今為止在異種移植研究中發(fā)現(xiàn)的豬，使我們更接近臨床試驗(yàn)階段，”蒙哥馬利博士說(shuō)?！拔覀冎肋@有可能挽救數(shù)千人的生命，但我們希望在前進(jìn)的過(guò)程中確保最大的安全和關(guān)懷。

GalSafe 是 Revicor， Inc. 的商標(biāo)。

媒體查詢

科林·德弗里斯 電話： 212-404-3588 colin.devries@nyulangone.org