-- -- ---

Tribune Online
Sickle cell: ‘So far so good, I hope it works, I hope she’s free of this disease’

This report by United States-based National Public Radio (NPR) details the story of a young Mississippi woman’s journey through a pioneering gene-editing experiment to ‘cure’ sickle cell disease.

 

When Victoria Gray was just 3 months old, her family discovered something was terribly wrong.

“My grandma was giving me a bath, and I was crying. So they took me to the emergency room to get me checked out,” Gray says. “That’s when they found out that I was having my first crisis.”

It was Gray’s first sickle cell crisis. These episodes are one of the worst things about sickle cell disease, a common and often devastating genetic blood disorder. People with the condition regularly suffer sudden, excruciating bouts of pain.

“Sometimes it feels like lightning strikes in my chest — and real sharp pains all over. And it’s a deep pain. I can’t touch it and make it better,” says Gray. “Sometimes, I will be just balled up and crying, not able to do anything for myself.

Gray is now 34 and lives in Forest, Miss. She volunteered to become the first patient in the United States with a genetic disease to get treated with the revolutionary gene-editing technique known as CRISPR.

NPR got exclusive access to chronicle Gray’s journey through this medical experiment, which is being watched closely for some of the first hints that changing a person’s genes with CRISPR could provide a powerful new way to treat many diseases.

“This is both enormously exciting for sickle cell disease and for all those other conditions that are next in line,” says Dr. Francis Collins, director of the National Institutes of Health.

“To be able to take this new technology and give people a chance for a new life is a dream come true,” Collins says. “And here we are.”

Doctors removed bone marrow cells from Gray’s body, edited a gene inside them with CRISPR and infused the modified cells back into her system this summer. And it appears the cells are doing what scientists hoped — producing a protein that could alleviate the worst complications of sickle cell.

“We are very, very excited,” says Dr. Haydar Frangoul of the Sarah Cannon Research Institute in Nashville, Tenn., who is treating Gray.

Frangoul and others stress that it’s far too soon to reach any definitive conclusions. Gray — and many other patients — will have to be treated and followed for much longer to know whether the gene-edited cells are helping.

“We have to be cautious. It’s too early to celebrate,” Frangoul says. “But we are very encouraged so far.”

Collins agrees.

“That first person is an absolute groundbreaker. She’s out on the frontier,” Collins says. “Victoria deserves a lot of credit for her courage in being that person. All of us are watching with great anticipation.”

This is the story of Gray’s journey through the landmark attempt to use the most sophisticated genetic technology in what could be the dawn of a new era in medicine.

Life filled with pain

When I first meet her, Gray is in a bed at the TriStar Centennial Medical Center in Nashville wearing a hospital gown, big gold hoop hearings and her signature glittery eye shadow.

It’s July 22, 2019, and Gray has been in the hospital for almost two months. She is still recovering from the procedure, parts of which were grueling.

Nevertheless, Gray sits up as visitors enter her room.

“Nice to meet y’all,” she says.

Gray is just days away from her birthday, which she’ll be celebrating far from her husband, her four children and the rest of her family. Only her father is with her in Nashville.

“It’s the right time to get healed,” says Gray.

Gray describes what life has been like with sickle cell, which afflicts millions of people around the world, including about 100,000 in the United States. Many are African American.

“It’s horrible,” Gray says. “When you can’t walk or, you know, lift up a spoon to feed yourself, it gets real hard.”

The disease is caused by a genetic defect that turns healthy, plump and pliable red blood cells into deformed, sickle-shaped cells. The defective cells don’t carry oxygen well, are hard and sticky and tend to clog up the bloodstream. The blockages and lack of oxygen wreak havoc in the body, damaging vital organs and other parts of the body.

Growing up, Victoria never got to play like other kids. Her sickle cells made her weak and prone to infections. She spent a lot of time in the hospital, recovering, getting blood transfusions — all the while trying to keep up with school.

“I didn’t feel normal. I couldn’t do the regular things that every other kid could do. So I had to be labeled as the sick one.”

Gray made it to college. But she eventually had to drop out and give up her dream of becoming a nurse. She got a job selling makeup instead but had to quit that too.

The sickle-shaped cells eventually damaged Gray’s heart and other parts of her body. Gray knows that many patients with sickle cell don’t live beyond middle age.

“It’s horrible — knowing that I could have a stroke or a heart attack at any time because I have these cells in me that are misshapen,” she says. “Who wouldn’t worry?”

Gray married and had children. But she hasn’t been able to do a lot of things most parents can, like jump on a trampoline or take her kids to sporting events. She has often had to leave them in the middle of the night to rush to the hospital for help.

“It’s scary. And it affected my oldest son, you know, because he’s older. So he understands. He started acting out in school. And his teacher told me, ‘I believe Jemarius is acting out because he really believes you’re going to die,’ “ Gray says, choking back tears.

Some patients can get help from drugs, and some undergo bone marrow transplants. But that procedure is risky; there’s no cure for most patients.

“It was just my religion that kind of kept me going,” Gray says.

An eager volunteer

Gray had been exploring the possibility of getting a bone marrow transplant when Frangoul told her about a plan to study gene editing with CRISPR to try to treat sickle cell for the first time. She jumped at the chance to volunteer.

“I was excited,” Gray says.

CRISPR enables scientists to edit genes much more easily than ever before. Doctors hope it will give them a powerful new way to fight cancer, AIDS, heart disease and a long list of genetic afflictions.

“CRISPR technology has a lot of potential use in the future,” Frangoul says.

To try to treat Gray’s sickle cell, doctors started by removing bone marrow cells from her blood last spring.

Next, scientists used CRISPR to edit a gene in the cells to turn on the production of fetal hemoglobin. It’s a protein that fetuses make in the womb to get oxygen from their mothers’ blood.

“Once a baby is born, a switch will flip on. It’s a gene that tells the … bone marrow cells that produce red cells to stop making fetal hemoglobin,” says Frangoul, medical director of pediatric hematology/oncology at HCA Healthcare’s TriStar Centennial Medical Center.

The hope is that restoring production of fetal hemoglobin will compensate for the defective adult-hemoglobin sickle cells that patients produce.

“We are trying to introduce enough … fetal hemoglobin into the red blood cell to make the red blood cell go back to being happy and squishy and not sticky and hard, so it can go deliver oxygen where it’s supposed to,” Frangoul says.

Then on July 2, after extracting Gray’s cells and sending them to a lab to get edited, Frangoul infused more than 2 billion of the edited cells into her body.

“They had the cells in a big syringe. And when it went in, my heart rate shot up real high. And it kind of made it hard to breath,” Gray says. “So that was a little scary, tough moment for me.”

After that moment passed, Gray says, she cried. But her tears were “happy tears,” she adds.

“It was amazing and just kind of overwhelming,” she says, “after all that I had went through, to finally get what I came for.”

The cells won’t cure sickle cell. But the hope is that the fetal hemoglobin will prevent many of the disease’s complications.

“This opens the door for many patients to potentially be treated and to have their disease modified to become mild,” Frangoul says.

The procedure was not easy. It involved going through many of the same steps as a standard bone marrow transplant, including getting chemotherapy to make room in the bone marrow for the gene-edited cells. The chemotherapy left Gray weak and struggling with complications, including painful mouth sores that made it difficult to eat and drink.

But Gray says the ordeal will have been worth it if the treatment works.

She calls her new gene-edited cells her “supercells.”

“They gotta be super to do great things in my body and to help me be better and help me have more time with my kids and my family,” she says.

 

Concerns about risk

Other doctors and scientists are excited about the research. But they’re cautious too.

“This is an exciting moment in medicine,” says Laurie Zoloth, a bioethicist at the University of Chicago. “Everyone agrees with that. CRISPR promises the capacity to alter the human genome and to begin to directly address genetic diseases.”

Still, Zoloth worries that the latest wave of genetic studies, including the CRISPR sickle cell study, may not have gotten enough scrutiny by objective experts.

“This a brand-new technology. It seems to work really well in animals and really well in culture dishes,” she says. “It’s completely unknown how it works in actual human beings. So there are a lot of unknowns. It might make you sicker.”

Zoloth is especially concerned because the research involves African Americans, who have been mistreated in past medical studies.

Frangoul acknowledges that there are risks with experimental treatments. But he says the research is going very slowly with close oversight by the Food and Drug Administration and others.

“We are very cautious about how we do this trial in a very systematic way to monitor the patients carefully for any complications related to the therapy,” Frangoul says.

Gray says she understands the risks of being the first patient and that the study could be just a first step that benefits only other patients, years from now. But she can’t help but hope it works for her.

She imagines a day when she may “wake up and not be in pain” and “be tired because I’ve done something — not just tired for no reason.” Perhaps she could play more with her kids, she says, and look forward to watching them grow up.

“That means the world to me,” Gray says.

It could be many weeks or even months before the first clues emerge about whether the edited cells are safe and might be working.

“This gives me hope if it gives me nothing else,” she says in July.

Heading home at last

About two months later, Gray has recovered enough to leave the hospital. She has been living in a nearby apartment for several weeks.

Enough time has passed since Gray received the cells for any concerns about immediate side effects from the cells to have largely passed. And her gene-edited cells have started working well enough for her immune system to have resumed functioning.

So Gray is packing. She will finally go home to see her children in Mississippi for the first time in months. Gray’s husband is there to drive her home.

“I’m excited,” she says. “I know it’s going to be emotional for me. I miss the hugs and the kisses and just everything.”

Gray is wearing bright red glittery eye shadow. It matches her red tank top, which repeats “I am important” across the front.

She unzips a suitcase and starts pulling clothes from the closet.

“My goodness. Did I really bring all this?” she says with a laugh.

Before Gray can finish packing and depart, she has to stop by the hospital again.

“Are you excited about seeing the kids?” Frangoul says as he greets her. “Are they going to have a big welcome sign for you in Mississippi?”

Turns out that Gray has decided to make her homecoming a surprise.

“I’m just going to show up tomorrow. Like, ‘Mama’s home,’ “ she says, and laughs.

After examining Gray, Frangoul tells her that she will need to come back to Nashville once a month for checkups and blood tests to see if her genetically modified cells are producing fetal hemoglobin and giving her healthier red blood cells.

“We are very hopeful that this will work for Victoria, but we don’t know that yet,” Frangoul says.

Gray will also keep detailed diaries about her health, including how much pain she’s experiencing, how much pain medication she needs and whether she needs any blood transfusions.

“Victoria is a pioneer in this. And we are very excited. This is a big moment for Victoria and for this pivotal trial,” Frangoul says. “If we can show that this therapy is safe and effective, it can potentially change the lives of many patients.”

Gray hopes so too.

“Not just for me, but for other people, this would be mind-blowing,” Gray says. “Oh my God. I can’t imagine the lives that could be saved if this thing actually works.”

Before she leaves, Gray has to let the nurses take a big blood sample for the study she is in. The trial is being conducted by CRISPR Therapeutics in Cambridge, Mass., and Vertex Pharmaceuticals in Boston. The project will eventually involve dozens of patients in the United States, Canada and Europe.

As the nurses fill one big vial after another, Gray talks about how she feels about having modified cells circulating in her body.

“I’m just genetically modified now,” she says with a giggle. “I’m a GMO. Isn’t that what they call it?”

Gray knows she’s about to start a limbo period of waiting to find out if her edited cells are working.

“I’m spiritual. And it’s something I prayed about,” she says. “And just the way everything happened for me, I just feel like it was fate for me to be here. So I just believe that God is doing this for me.”

The big reveal

It’s a foggy morning a few weeks later. Gray steps out of her car in a parking garage at the hospital. She just drove back to Nashville after spending about a month at home in Mississippi.

“I feel good,” she says. “I’m hoping to get some good news today.”

Frangoul should have some results from her latest blood tests about whether her genetically modified cells are working.

Gray says she’s not nervous, except “about the needles.” She will have to go through another big blood draw today.

For this visit, Gray is wearing a black sweatshirt with big letters that spell out “Warrior.”

“They call sickle cell patients warriors, and I saw this shirt at Walmart so I had to get it,” she says as she heads over to give her blood sample.

As the nurses fill one big tube after another, Gray describes her homecoming a few weeks earlier.

“It was emotional for me, because I love them so much,” she says, stifling tears. “I did this for them. So it’s worth it.”

The nurses are finally done. Gray heads over to see her doctor.

“I’m terribly excited about your bloodwork today,” Frangoul says.

After a quick physical exam, Frangoul shows Gray what she’d been waiting for: The results of some of her blood tests.

“So look at this,” says Frangoul, smiling, as he hands her a sheet of paper. “This is very exciting. I am super-excited about your results today.”

Gray’s CRISPR-edited cells seem to be working.

“It looks like there are signs that you are starting to make fetal hemoglobin, which is very exciting for us,” Frangoul says.

Nearly half the hemoglobin in Gray’s blood is now fetal hemoglobin, which is more than doctors think is needed to help alleviate the complications of sickle cell. And the level of that protein seems to be continuing to rise.

“Oh my goodness,” Gray says.

The treatment also still seems safe, so far. There have been no signs of any ill effects from the modified cells.

In addition, there are clues that the cells could already be helping Gray. She hasn’t needed any blood transfusions since she got the cells, hasn’t had any pain attacks and hasn’t had to rush to the hospital for help.

“That’s good. Excellent. Perfect,” Frangoul says. “This is extremely encouraging.”

Typically, Gray says, she would have had another pain episode by now.

“I would have had at least had something,” she says.

“It’s special, especially coming up on the holidays — because sometimes I would be in the hospital on Christmas,” Gray says. “So I’m looking forward to a whole new life for all of us.”

Other hopeful signs

The same kind of CRISPR gene-edited cells seem to be helping a patient who received them in Germany for a related genetic blood disorder called beta thalassemia.

But Frangoul knows he still must remain cautious.

“It is still too early to celebrate. I just want to make sure this is something we watch very carefully every visit and see how things are going,” he says.

Doctors will have to follow Gray for years and study many additional patients to answer the most important questions: Are the cells really helping patients live healthier lives? Will they keep working? Will they keep working safely? And will the cells actually help patients live longer?

“This would be life-changing, not only for Victoria but for many sickle cell patients,” Frangoul says. “Because if this is determined to be safe and effective, I think it can be transformative for patients with sickle cell disease.”

Other genetic therapies are also showing promise for sickle cell. So researchers have already started to try to make such expensive, complicated treatments practical and affordable, especially in poor countries. That’s where diseases such as sickle cell are most common.

“The progress that we’ve seen for sickle cell disease, including Victoria Gray and her involvement in this, made it clear that if this is starting to work, we need to get busy and figure out how to take it to the next level,” says Collins, the NIH director.

Zoloth, the University of Chicago bioethicist, says she’s encouraged to see progress for a disease that has long been neglected. But she’s still cautious about the research, especially because only one patient has been treated, and so recently. She worries about raising false hope.

“So far so good,” Zoloth says. “And of course that’s great news. I hope it works. I hope she’s free of this disease, and I hope this very, very brave woman has a life of joy and freedom from pain and can raise those beautiful children.”

But, she adds, “it’s still very early days. We’re still waiting for real news — which is, ‘This is the definitive cure. This will help many, many thousands of people.’ It would be a wonderful thing for humanity.”

Other doctors are using CRISPR to try to treat cancer. One team soon plans to try to edit genes inside the body for the first time — modifying genes in retinal cells of the eye to try to restore vision to people blinded by a rare genetic disorder.

Gray knows this is just the beginning. But she’s happy things are going well so far.

“It’s amazing to have a chance at a different type of life,” Gray says. “It’s a miracle. When you pray and ask God for something for so long, all you have left is hope.”

Gray has already started doing things she could never do before, such as go to one of her son’s football games for the first time.

“I don’t really want anything extravagant,” she says. “I just want a simple life with my family and the people who I love and people that love me — and just live, you know?” Gray says. “This could be the beginning of something special.”

Source: National Public Radio Inc. US (NPR.org).

 

 

Sickle cell: ‘So far so good, I hope it works, I hope she’s free of this disease’
Tribune Online



source https://tribuneonlineng.com/sickle-cell-so-far-so-good-i-hope-it-works-i-hope-shes-free-of-this-disease/

Post a Comment

Previous Post Next Post
__