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CRISPR for sickle cell disease shows promise in the early test: shots



Victoria Gray (center) took blood samples from nurses Bonnie Carroll (left) and Kayla Jordan at the TriStar Centennial Medical Center, Nashville, Tenn, in a clinical study to treat sickle cell disease.

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Blood samples were taken from nurses Bonnie Carroll (left) and Kayla Jordan at the TriStar Centennial Medical Center, Nashville, Tennessee, as part of a clinical trial to treat sickle cell disease.

Meredith Rizzo / NPR

Doctors report the first evidence that genetically modified cells could provide a safe way to treat sickle cell disease, a devastating, incurable disorder that affects millions of people around the world.

Billion Cells That Have Been Genetically Modified According to high-profile data released on Tuesday, CRISPR, a powerful gene-editing technique, has begun to work as doctors had hoped in the body of the first sickle-cell patient, who received the experimental treatment.

The Processed Cells Produce a Critical Protein To an extent beyond what physicians considered necessary to alleviate the agonizing, life-threatening complications of genetic blood disease, the early data shows. In addition, the cells appear to have already spared the patient from the agonizing pain attacks that are the hallmark of the disorder.

"We are very, very excited," says Dr. Haydar Frangoul of the Sarah Cannon Research Institute in Nashville, Tenn., Who treats the patient. "This preliminary data shows for the first time that editing genes has actually helped a sickle cell patient, which is definitely a big deal."

However, Frangoul and other researchers warn that the results only affect one patient, who was recently treated. It is far too early to answer the most important questions: Does the treatment with modified cells continue to improve the patient's health? Does the treatment continue? Will it help her to live longer? Is it safe in the long term?

"We hope it is," says Frangoul, a success. But "it is still too early to celebrate."

NPR has exclusive access to the chronicle of the experience of Frangoul's patient Victoria Gray of Forest, Miss., The first person with a genetic condition treated with CRISPR in the US.

Frangoul recently said with a smile when he showed her latest blood test results to Gray. The tests showed that the genetically engineered cells had already produced the key protein to the extent that doctors hope will relieve their suffering. "I am very excited about your results today," said Frangoul. He recovered from the medical procedure, which used an experimental technique called CRISPR to process the genes of their own bone marrow cells.

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In July, Gray recovered from the medical procedure, which used an experimental technique called CRISPR to process the genes of their own bone marrow cells.

Meredith Rizzo / NPR

Although Gray knows it is still very early, she described how the treatment seems to help her. She has not suffered any of the painful attacks that torture sickle cell patients, and has not had to go to hospital since receiving the modified cells this summer. She also did not need blood transfusions and has begun to reduce the chronic painkillers.

"It's a miracle," says Gray, who for the first time hopes for a life of tormenting pain and debilitating, life-threatening complications of the disease. Sickle cell disease is a hereditary disease characterized by defective oxygen-carrying red blood cells.

"If you pray for something for so long, you can only have hope," says Gray, 34, who has four children. "It is amazing."

Initial research has been published by the two companies that sponsored the study for which Gray volunteered, Vertex Pharmaceuticals in Boston and CRISPR Therapeutics in Cambridge, Massachusetts.

"This is a very important scientific work and medical milestone," Dr. Jeffrey Leiden, Chairman, President and CEO of Vertex. "We may have cured this patient with a single treatment and we are very confident."

While Gray had some complications after treatment, she recovered. According to the companies, none of the problems has been caused by the treatment itself.

"I find it tremendously exciting that we have reached a point where gene editing with CRISPR is being applied to sickle cell disease." Francis Collins, director of the National Institutes of Health. Collins, who is not involved in the research, found that about 100,000 people in the US are affected by sickle cell disease and millions more worldwide.

"Being able to use this new technology and giving those people the chance to start a new life" Collins says that a dream has come true. "

Because of the promise of such research, the National Institutes of Health partnered with the Bill & Melinda Gates Foundation over $ 200 million to find ways within 10 years to make expensive, complex gene-based treatments affordable and convenient in poor countries where diseases like sickle cells are most common (The Gates Foundation supports reporting on global health and development by NPR.)

"The progress we have seen in gene therapy approaches to sickle cell disease in the US, including Victoria Gray and her involvement in this gene -Editiation protocol, made it clear that it was time to start in the next phase, "said Collins this is starting to work – but does not work, where most patients are, what is Africa – we need to get busy and take it to the next level. "just announced that the first patient in the study had been treated and that another Patient with a related blood disorder who had beta-thalassemia, received CRISPR treatment this year and had not needed a blood transfusion for four months.

Treatment treatment at the Sarah Cannon Research Institute in Nashville, Tenn.

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Gray received genotoxic treatment at the Sarah Cannon Research Institute in Nashville, Tennessee.

Meredith Rizzo / NPR

That's true after the new data even after nine months. The beta thalassemia patient treated in Germany has not been publicly identified. Typically, beta thalassemia patients require regular transfusions to survive. According to the companies, the CRISPR-treated patient usually needed more than 16 transfusions per year. This patient also had health problems after treatment, but also recovered and it is thought that none of them were caused by the treatment.

"This is the first evidence that the new CRISPR technology has the potential to cure serious genetic problems in humans." David Altshuler, the scientific director of Vertex.

"And this is just the beginning of this new type of therapy, and its applications may go beyond sickle cell disease and beta-thalassemia and affect other genetic diseases."

Many researchers believe CRISPR could revolutionize medicine. The technique allows scientists to make DNA changes much easier than ever before.

Doctors are also trying to use CRISPR to treat cancer. Most of this research is done in China, and almost no results have been reported. But the University of Pennsylvania, which has tested CRISPR in three cancer patients, recently reported that gene manipulation seems feasible and safe. Another study recently started recruiting cancer patients in the US and Australia.

Later this year, Boston physicians plan to use CRISPR for the first time to manipulate cells while still in the patient's body – the retina – in the hope of restoring vision in patients with congenital blindness ,

When NPR interviewed Gray, she had just returned to Nashville for five hours after spending about a month at home with her family in Mississippi. She had been in Nashville for about three months this summer to undergo surgery on 2 July and then recover from the treatment that required the equivalent of a bone marrow transplant.

During the return visit, Gray wore a black hooded sweatshirt with the words "Warrior" on the front.

"You know, they call sickle-cell patient warriors, and I've seen this shirt at Walmart, so I had to get it," says Gray. "It's a constant fight."

Sickle cell disease is a cruel genetic disorder that deforms red blood cells into defective crescent-shaped cells. The cells clog the bloodstream, damage vital organs and cause countless health problems, in addition to attacks of severe pain. Many patients with the disease can not work or go to school. Many die of complications such as heart attack and stroke before reaching middle age.

Researchers warn that Gray's results are preliminary as they only affect one patient. There is still a lot of unknown, including the question of whether the treatment will sustainably improve Gray's health and whether it will be safe in the long term.

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Researchers warn that Gray's results are preliminary as they only affect one patient. There is still much unknown information, including whether the treatment will sustainably improve Gray's health and whether it will be safe in the long term.

Meredith Rizzo / NPR

"I had moments when I only stood and laughed [and] and talked to friends Next, my husband had to carry me to the ER because I could not use my legs because they hurt so bad," says Gray, who has already suffered heart damage from her illness.

"And if you can not help it, it's just one of those things that just makes you give up," she says voice breaks down with emotion.

Before Gray saw Frangoul, TriStar Centennial Medical Center nurses took 16 ampoules of blood for testing as part of the clinical trial. The trial will ultimately involve 45 patients in the US, Canada and Europe. The beta-thalassemia study will ultimately affect 45 patients in Canada, Germany and London.

When the nurses filled one big tube of blood after another, Gray described her return home a few weeks earlier.

"My eldest son – when he took it twice and realized that I was in the car – he ran off and he grabbed me and held me tight and the twins saw me from inside the house, my mother said that My daughter was, "My mom is out there." She just jumped, they knew it was mom, "she says. "It's emotional to me, you know, because I love her so much, I did it for her, so it's worth it."

After Gray had given her 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 some evidence that you are starting to make fetal hemoglobin, which is very exciting," said Frangoul.

Fetal hemoglobin is a protein that is normally only produced by fetuses and newborns for a short time after birth. The scientists used CRISPR to process a gene in bone marrow cells that had been removed from Gray's body.

The processed cells were re-infused into their system, and the modification of the processing enabled the cells to produce fetal hemoglobin again. The hope is that fetal hemoglobin compensates for the genetic defect that has led to sickle cell disease and its abnormal form of adult hemoglobin.

The processed cells began to function in Gray's body about a month after the infusion. Four months after Gray received the cells, her blood tests revealed that 46.6% of hemoglobin in her system is fetal hemoglobin, according to the company. This exceeds the 20% to 30% that doctors found necessary to help her. And her fetal hemoglobin levels are still rising, Frangoul said in an interview. In addition, 94.7% of the erythrocytes of Gray contain fetal hemoglobin, companies reported.

After the strenuous procedure, Gray suffered from a blood infection, gallstones, and abdominal pain that corresponded to a bone marrow transplant. The beta thalassemia patient developed pneumonia and a liver problem. However, it is believed that none of these complications were caused by the processed cells.

Other researchers are testing a different approach to sickle cells that uses a virus to insert a healthy gene into the cells of sickle cell patients. This approach is also promising. Scientists also plan to use CRISPR to correct the defective gene itself, which would be more difficult.

Frangoul stresses that it is still too early to know if fetal hemoglobin production will continue and how this could help Gray over a longer period of time.

"I just want to make sure that this is something we watch closely every time we visit and see how things go," he told Gray.

But Frangoul, medical director of pediatric hematology / oncology at HCA The TriStar Centennial Medical Center in Healthcare knows that Gray is doing better.

"You have not been in the hospital since I last saw you, right?" he said. "No emergency room, no hospitals, how about that? That's good. Excellent. Perfect. That's very encouraging."

While Frangoul says that some sickle cell patients can get along without severe pain attacks for a long time, Gray usually says that she has suffered a kind of episode in the time since receiving the processed cells. In the two years prior to treatment, Gray had seven sickle cell crises per year.

In a recent research, Dr. Haydar Frangoul Gray preliminary results that showed that her body produces fetal hemoglobin, a protein that can relieve the symptoms of her sickle cell disease.

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In a recent research, Dr. Haydar Frangoul Gray preliminary results showing that her body produces fetal hemoglobin, a protein that could alleviate the symptoms of her sickle cell disease.

Meredith Rizzo / NPR

"It's special, especially on holidays, because I sometimes go to the hospital for Christmas, so I'm looking forward to a whole new life for all of us," she said.

Gray calls processed cells their "supercells".

"They seem to be great," Gray said with a laugh.

Frangoul wants to follow Gray for many more months to see if her "super-cells" are making her healthier and longer, to see if they can help her live longer. Researchers plan to examine Gray and other subjects for 15 years to ensure that the cells themselves do not cause long-term side effects.

"This would change life not only for Victoria, but for many sickle cell patients as well," said Frangoul. "If this is considered safe and effective, it may be transformative for patients with sickle cell disease."

Prior to treatment, Gray was so weakened by her illness that she could not work or go to school, and she was unable to attend many of her children's activities.

Since treatment, she has felt strong enough to attend her son's football game for the first time. She hopes that she may now spend much more time with her children and see her growing up.

"I do not want anything extravagant," said Gray. "I just want a simple life with my family and the people I love and love, and I just want to live, you know, this could be the start of something special."


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