Meredith Rizzo / NPR
Doctors report the first evidence that genetically engineered cells could offer a safe way to treat sickle cell disease, a devastating, incurable disorder that affects millions of people around the world.
Billions of cells that were genetically modified by a powerful gene editing technique called CRISPR began working as doctors hoped inside the body of the first sickle cell patient to receive experimental treatment, according to highly anticipated data released Tuesday .
Edited cells produce crucial protein at levels already beyond what doctors thought were necessary to alleviate the excruciating, life-threatening complications of genetic blood disease, early data show. It also appears that the cells have already begun to spare the patient from agonizing pain attacks, which are a hallmark of the disorder.
"We are very, very excited," says Dr. Haidar Frangul of the Sarah Ken Research Institute in Nashville, Tenn., Who is treating the patient. "This preliminary data shows for the first time that gene editing actually helped a patient with sickle cell disease. It's definitely a huge deal."
However, Frangul and other researchers warn that the results include only one patient who has only recently been treated. It is too soon to answer the most important questions: Will continued treatment with modified cells improve the patient's health? Will the treatment continue to work? Will it help her to live longer? Is it safe in the long run?
"We hope it is" a success, Frangul says. But "it's still too early to celebrate."
NPR has exclusive access to the chronicle of the experience of Frangul's patient, Victoria Gray of Forrest, Miss., The first person with a genetic disorder to be treated with CRISPR in the United States.
"So look at this" Frangul said recently with a smile as she showed Gray her latest blood test results. The test showed that genetically modified cells have already begun to produce the crucial protein at levels that doctors hope will alleviate her suffering.
"Today, I'm very excited about your results," Frangul said.
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Although Gray knew it was still too early, she described what treatment seemed to be helping her. She has not suffered any of the painful attacks that plague patients with sickle cell cells and has not needed to rush to the hospital since she received the modified cells this summer. She also did not need blood transfusions and began to reduce pain medication she was taking chronically.
"It's a miracle," says Gray, who says there is hope for the first time in his entire life to fight excruciating pain and disabling, life-threatening complications of the disease. Sickle cell disease is a hereditary condition that is marked by defective red blood cells that carry oxygen.
"When you pray for something that long, all you can have is hope," says 34-year-old Gray, who has four children. "It's amazing.
The early results of the study were published by the two companies sponsoring the study, which Gray volunteered for, Vertex Pharmaceuticals in Boston and CRISPR Therapeutics in Cambridge, Massachusetts
." This is a very important scientific and medical point "said Dr. Jeffrey Lydon, President, President and CEO of Vertex." We have a potential cure for this one-time patient. We hope very much. "
While Gray experiences some complications after treatment, she recovers, and none of the problems are caused by the disease itself. treatment, according to the companies.
"I think it's extremely exciting that we have reached the point where gene editing using CRISPR is applied to sickle cell disease," says Dr. Francis Collins, director of National Health institutes. Collins, who did not participate in the study, noted that sickle cell disease affects about 100,000 people in the United States and millions more around the world.
"To be able to use this new technology and give these people a chance for a new life, which it really would be, is a dream come true," Collins says.
Because of the promise of such research, National Institutes of Health are starting a partnership with $ 200 million with the Bill and Melinda Gates Foundation to find ways, within 10 years, to make expensive, complex gene treatments affordable and practical in poor countries where sickle cell disease is most common. (Gates Foundation provides support for reflecting a fine NPR.)
"The progress we have seen in gene therapy approaches to sickle cell disease in the United States, including Victoria Gray and her involvement in this gene-editing protocol, has made it clear that time to start the next phase of this, "Collins said. "If that starts to work – but it won't work where most patients are, which is Africa – we need to get on with it and take it to the next level."
Sickle cell research companies had previously revealed only that the first patient in the study had been treated and that another patient with a related blood disorder, beta thalassemia, had undergone CRISPR treatment this year and did not need it. from a transfusion for four months.
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This is still true after nine months, according to new data. The patient with beta thalassemia treated in Germany has not been publicly disclosed. Typically, patients with beta thalassemia need regular transfusions to survive. Patients treated with CRISPR typically require more than 16 transfusions each year, according to the companies. This patient also had health problems after treatment, but also recovered and was not thought to be caused by treatment.
"This is the first evidence that new CRISPR technology in humans can be treated for serious genetic diseases," says Dr. David Altshuler, Chief Scientific Officer of Vertex.
"And this is only the beginning of this new type of therapy. Its applications may go beyond sickle cell disease and beta thalassemia to other genetic diseases. "
Many researchers believe that CRISPR can revolutionize medicine. The technique allows scientists to make very accurate DNA changes much easier than ever.
Doctors are also trying to use CRISPR to treat cancer. Most of these studies are in China and almost none of the results have been reported, but the University of Pennsylvania, which tried CRISPR on three cancer patients, recently reported that genetic editing seems possible and safe. recruiting cancer patients
Later this year, Boston doctors plan to use CRISPR for the first time to edit cells while they are still in patients' bodies – in the retinas – with the hope of restoring vision in patients with
When NPR interviewed Gray most recently, she had just driven five hours back to Nashville after spending about a month home in Mississippi with her family. She was in Nashville for about three months in the summer to undergo the procedure on July 2 and then recover from treatment, which requires a bone marrow transplant equivalent.
During the return visit, Gray wore a black hooded sweatshirt emblazoned with the word "warrior" in the front.
"You know, they call sickle cell warriors, and I saw this Walmart shirt, so I had to get it," Gray says. "It's a constant battle."
Sickle cell disease is a cruel genetic disease. a disorder that deforms red blood cells into defective sickle cells The cells clog the circulatory system, damaging vital organs and causing many health problems in addition to severe pain Many patients with the disease cannot work or go to school Many minds
Meredith Rizzo / NPR
"I had moments where I just stood there, laughing [and] talking to friends, and then the next thing you know, my husband had to carry me to the emergency room because I couldn't use my feet because they hurt me so bad, "says Gray, who has already suffered heart damage from his illness.
"And when you can't help it, it's just one of those things that just makes you want to give up," she says.
Before Gray saw Frangoul, nurses at TriStar Metropolitan Medical Center 16 vials of blood for testing as part of a clinical trial. The study aims to reach 45 patients in the US, Canada and Europe. The beta thalassemia trial is intended to include 45 patients in Canada, Germany and London.
While the sisters were filling one large blood tube after another, Gray described his home a few weeks earlier.
"My eldest son – when he did his double take and found out I was in the car – he took off running and he just grabbed me and threw himself at me. And the twins saw me inside the house. My mom told me that my daughter is: "My mother is out. "She was just jumping. They knew it was Mom," she says. "It's emotional for me, you know, because I love them so much. I did it for them. So, it's worth it."
After Gray did a blood test, she met with Frangoul, who gave her a short physical exam before showing her a piece of paper with her latest test results.
"There seems to be signs that you're starting to take fetal hemoglobin, which is very exciting," Frangul said.
Fetal hemoglobin is a protein that is usually produced only by fruits and newborns shortly after birth. Thus, scientists used CRISPR to edit a gene in bone marrow cells that had been removed from Gray's body.
The edited cells flow back into her system and the change in editing allowed the cells to start producing fetal hemoglobin again. It is hoped that fetal hemoglobin will compensate for the genetic defect that led to sickle cell disease and its abnormal form of hemoglobin in adults.
The edited cells begin to function about a month after they flow into Gray's body. Four months after Gray received the cells, her blood tests showed that 46.6% of the hemoglobin in her system was fetal hemoglobin, according to the companies. This goes far beyond the 20% to 30% that doctors thought would be needed to help her. And her fetal hemoglobin levels are still rising, Frangul said in an interview. In addition, 94.7% of Gray's red blood cells contain fetal hemoglobin, the companies said.
Gray suffered a blood infection, gallstones and abdominal pain after a debilitating procedure that included the equivalent of a bone marrow transplant. The patient with beta thalassemia developed pneumonia and a liver problem. But none of these complications are thought to be caused by the edited cells.
Other researchers are testing another approach for sickle cells, which involves the use of a virus to insert a healthy gene into the cells of sickle cell patients. This approach also shows promise. Scientists also plan to try using CRISPR to correct the defective gene itself, which would be more difficult.
Frangoul emphasizes that it is too early to know whether the production of hemoglobin in the fetus will continue and how it can help Gray's health for a longer time
"I just want to make sure it's something which we look at very closely every visit and see how things are going, "he told Gray.
But Frangul, medical director of pediatric hematology / oncology at HCA TriStar Centennial Health Center, knows that Gray is feeling better.
"You haven't been to the hospital since I last saw you, have you?" he said. "There are no emergency rooms, no hospitals. How about that? That's good. Great. Perfect. That's extremely encouraging."
While Frangul says that some patients with sickle cells can go on for long periods without severe attacks of pain, Gray says that she would normally undergo some sort of episode in the period since she received the edited cells. In the two years prior to treatment, Gray experienced seven sickle cell crises a year.
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"This is special, especially when it comes to the holidays, because sometimes I would be in the hospital at Christmas. So I look forward to a new life for all of us," she said.
"They seem to be super after all," Gray said and laughs.
Frangul plans to follow Gray for many more months to see if her "supercells" really make her healthier, and even longer to see if they help her live longer. The researchers plan to check for Gray and other research topics for 15 years to make sure that the cells do not cause any of their own long-term side effects.
"This would change lives not only for Victoria, but for many sickle cell patients," Frangul said. "If this is determined to be safe and effective, I think it can be transformative for patients with sickle cell disease."
Prior to treatment, Gray was so weak from her illness that she could not work or go to school and was unable to participate in many of her children's activities.
After treatment, she felt strong enough to go to one of her son's football games for the first time. She hopes that she may now be able to spend much more time with her children and see them grow up.
"I don't really want something extravagant," Gray said. "I just want a simple life with my family and the people I love and the people who love me and just live, you know? This may be the beginning of something special. "