Genetically Altered Skin Saves A Boy Dying Of A Rare Disease-转基因皮肤挽回了一个危殆的男孩
In the future, we may not need to rely on human donations for life-saving skin grafts.
November 8, 20171:28 PM ET
Heard onAll Things Considered
That’s the goal of XenoTherapeutics, a Boston-based biotech nonprofit. Last week, the US Food and Drug Administration approved the group’s initial application for temporary skin grafts curated from genetically modified pigs. This means that they can start testing pig skin grafts on people who have experienced severe burns. It’s the first time that an animal organ has been cleared for human testing in the US.
Skin, the body’s largest organ, plays a crucial role in the immune system by blocking pathogens from reaching our vulnerable internal organs. It also holds in water, electrolytes, and other nutrients, and helps the body maintain a constant temperature. People with severe skin damage are at a high risk of developing deadly infections or organ failure as a result of changes in temperature or hydration.
grew sheets of genetically altered skin cells in the lab and used them
Skin grafts can help protect these patients as they heal. At the moment, the only skin grafts available in the US come from cadavers who have agreed to be organ donors, or patients who have undergone surgery to remove excess skin after dramatic weight loss. These human skin used for grafts are a “rare commodity.”
to treat a boy withlife-threatening epidermolysis bullosa.
XenoTherapeutics, which gets its name from xenotransplantation, or animal-to-human transplants, has bred pigs that have skin remarkably similar to our own. Although pig skin normally produces a type of sugar human skin does not, these pigs have been genetically modified not to make it. Grafts from these pigs are therefore more likely to slide under the radar of the host’s immune system—at least temporarily. The idea is that they could be used for immediate burn treatment, followed human skin graft treatment later.
“I would venture that if we did a Coke and Pepsi side-by-side comparison… you’d be hard-pressed to tell which was the human cadaveric allograft versus [the pig graft],” said XenoTherapeutics CEO Paul Holzer.
child who was on the verge of death from a rare inherited disease has
been treated with genetically engineered skin cells that replaced most
The nonprofit has been working closely with physicians at Massachusetts General Hospital, who will help conduct the clinical trials starting next month. The first trial will only be testing the grafts’ safety and tolerability in six patients with severe burns. Assuming the results are positive after a month, the grafts will need to undergo two more stages of testing before they can be approved for widespread clinical use.
of the skin on his body.
Several other groups around the world are working to make animal organs suitable for clinical medicine. In Brazil, researchers are exploring using tilapia skin for use as temporary bandages for burn victims whose skin is regrowing. Just last week, scientists from Germany reported that they had made a crucial step in keeping baboons given genetically modified pig hearts alive for half a year. Their success suggests that pig hearts could one day be used to treat patients with heart failure.
treatment represents a notable success for the field of genetherapy,
which has suffered manysetbacks. And it's potentially good news for
children suffering from a painful and often deadly skin condition called
this disease, children are born with a flawed gene that prevents the
outer layer of the skin, theepidermis, from binding to the inner layer.
This can cause excruciatingblistersto form all over these children's
the case in Europe, a 7-year old boy ended up in the hospital back in
2015 after 60 percent of his epidermis had sloughed off. Tobias
Rothoeft, a surgeon at a burn unit at Ruhr University in Bochum,
Germany, says he and his colleagues tried everything — including a skin
transplant from the boy's father —to no avail.
在澳大澳门联邦（Commonwealth of Australia）的贰个病例，一个7岁的男孩住进了卫生院，二零一四年后他的四分之一的肌肤已经脱落。TobiasRothoeft，在波鸿的鲁尔大学的一名黄疸科医务职员德意志联邦共和国说，他和他的同事们品尝了全套——满含男孩阿爹的肌肤移植——但都不行。
"After nearly two months we were absolutely sure there was nothing we could do for this kid and that he would die," Rothoeft said in a telephone news conference hosted byNature, which publishedthe studyonline Wednesday.
Rothoeft and his colleagues took one last look around the medical literature and learned of researchers in Italy who were experimenting with anew treatment00126-4)for this disease. Michele De Luca and colleagues at the University of Modena and Reggio Emilia were genetically engineering skin cells to repair the inborn flaw.
Rothoeft和她的同事们不常见到了一份医学文献，获悉意大利共和国的钻探人口正在考试治疗这种病痛的新的看病措施。来自意大利共和国摩德纳大学Michele De Luca和Cole正选取基因工程的肌肤细胞修复基因的原状缺欠。
Luca used a virus toinserta healthy gene into cells taken from the
boy's skin. Some of those cells,stem cells,multiply indefinitely. So De
Luca was able to grow entire sheets of engineered epidermis, which were
shipped to the hospital in Germany.
De Luca用一种病毒将常规的基因插入从男孩皮肤中抽出的细胞中。在那之中一些细胞，干细胞，无有效期繁衍。所以De 卢卡能够一整面包车型大巴转基因的人工表皮，它被运往了德意志联邦共和国的卫生院。
Luca had used this procedure successfully in 2006 to replace a
relatively small patch of skin on another patient. But this boy needed
to have 80 percent of his skin replaced with grafts of this genetically
modified material. It took two operations, both in the fall of 2015.
the first one, we grafted all four limbs," De Luca told reporters in
the press call. "In the second operation we grafted the remaining part
of the body, mainly the back."
eight months in the intensive care unit, the boy was well enough to go
home. And, two years later, he is in school, even playing soccer.
kid is doing quite well," Rothoeft said. "The skin is of good quality,
it doesn't need any ointments or stuff like that. It's perfectly smooth
and it is quite stable. And if he gets any bruises, they
justheallikebruisesin every other kid."
Onelingeringquestion is the concern that gene therapies like this, involving viruses, can increase the risk of cancer. That's because the viruses insert the new gene randomly into human DNA. Anattemptat using gene therapy to treat severe combined immuneodeficiency (SCID) in 2002 ended up triggering cancer in some patients.
That bad result set back the field of gene therapy, though there have since been successes treatingSCID, and most recently, cancer.
it is a potential problem," De Luca said. But he generated hundreds of
millions of cells during this procedure and didn't see anything of
concern. And in this case, clearly the benefits of treating the boy
outweighed the risks.
News of this is just starting to trickle out to advocates who have children with epidermolysis bullosa.
"I think it's groundbreaking," says Brett Kopelan, who heads a U.S. organization focused on this disease, known by its acronym,debra. "I think it's incredibly exciting."
His 10-year-old daughter Rafi has a severe case.
Kopelan, 10, has epidermolysis bullosa, which causes painful blisters
of the skin and mucous membranes. Her father, Brett, is at right.
Courtesy of Brett Kopelan
the last time you had a paper cut and you put some Purell on it and it
stung, right?" Kopelan says. "Now imagine that being 60 percent of your
you have to do a bath and bandage change every day, you are subjected
to severe torture. It's incredibly painful, and it can take up to 3 to 4
hours a day," he says. "As a parent, there's not a day that goes by
that a little bit of my heart doesn't break.
Rafi, knowing that it's going to be an incredibly painful couple of
hours, walks into the bath and bandage room ... so that we can clean her
wounds to make sure they don't get infected and to prevent a
potentially life-threatening situation.
"She's the bravest person I know."
addition to the painfulblisters, Rafi needs frequent throat surgeries,
because her condition also affects mucous membranes. She often uses a
wheelchair because it's so painful to walk.
daughter would love to be able to not have to wear bandages on a daily
basis, she'd love to jump in a pool without worrying about it hurting,
or taking a shower — or even wearing shoes."
The skin therapy described in theNaturepaper wouldn't cure her — in fact, it targets a different genetic defect that causes the same condition. But a similar approach could reduce the agony of daily living. And Kopelan says medical interest in this disease is now growing rapidly.
gone from zero biotechnology and pharmaceutical [companies] to like 12
companies, so we're really at aninflectionpoint right now," he says.
Experimentaltreatments are getting under way in the United States and Asia, as well as in Europe. Peter Marinkovich, Jean Tang and colleagues at the Stanford University School of Medicine areusing the same approachas De Luca, and they have treated seven children using smaller patches of skin.
U.S.A.和南美洲以致亚洲正值扩充试验性治疗。Peter 马林kovich，姬恩Tang和她的同事们在巴黎综合理历史高校经济高校使用和De Luca同样的点子，用小块皮肤医疗了四个儿女。
tells Shots that their long-term goal is to treat a child's entire
body, and the research is gradually laying the groundwork to do that.
The severely injured child in Germany offered a unique opportunity to
try that, and the encouraging results are generating more enthusiasm. "I
was super impressed when I saw [the] results," Marinkovich says.
原稿来自 NP汉兰达Richard HarrisNovember 8, 20171:28 PM ET