Sickle Cell Therapy With CRISPR Gene Editing Shows Promise : Shots – Invest Records

Posted: December 27, 2019 at 1:41 pm

Victoria Gray, who has sickle cell disease, volunteered for one of the most anticipated medical experiments in decades: the first attempt to use the gene-editing technique CRISPR to treat a genetic disorder in the United States.

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Victoria Gray, who has sickle cell disease, volunteered for one of the most anticipated medical experiments in decades: the first attempt to use the gene-editing technique CRISPR to treat a genetic disorder in the United States.

Meredith Rizzo/NPR

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. Thats when they found out that I was having my first crisis.

It was Grays 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 its a deep pain. I cant 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 Grays journey through this medical experiment, which is being watched closely for some of the first hints that changing a persons 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 Grays 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 its 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. Its too early to celebrate, Frangoul says. But we are very encouraged so far.

Collins agrees.

That first person is an absolute groundbreaker. Shes 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 Grays journey through the landmark attempt to use the most sophisticated genetic technology in what could be the dawn of a new era in medicine.

The study took place at HCA Healthcares Sarah Cannon Research Institute and TriStar Centennial Medical Center, in Nashville, Tenn., one of 11 sites recruiting patients for the research in the U.S., Canada and Europe.

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The study took place at HCA Healthcares Sarah Cannon Research Institute and TriStar Centennial Medical Center, in Nashville, Tenn., one of 11 sites recruiting patients for the research in the U.S., Canada and Europe.

Meredith Rizzo/NPR

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.

Its 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 yall, she says.

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

Its 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.

In July, Gray was recovering after a medical procedure that infused billions of her own bone marrow cells back into her body after they had been modified using the gene-editing technique CRISPR. Her father, Timothy Wright (right), traveled from Mississippi to keep her company.

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In July, Gray was recovering after a medical procedure that infused billions of her own bone marrow cells back into her body after they had been modified using the gene-editing technique CRISPR. Her father, Timothy Wright (right), traveled from Mississippi to keep her company.

Meredith Rizzo/NPR

Its horrible, Gray says. When you cant 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 dont 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 didnt feel normal. I couldnt 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 Grays heart and other parts of her body. Gray knows that many patients with sickle cell dont live beyond middle age.

Its 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 wouldnt worry?

Gray says she understands the risks involved in the treatment. This gives me hope if it gives me nothing else, she says.

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Gray says she understands the risks involved in the treatment. This gives me hope if it gives me nothing else, she says.

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Gray married and had children. But she hasnt 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.

Its scary. And it affected my oldest son, you know, because hes 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 youre 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; theres 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 Grays 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. Its 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. Its 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 Healthcares 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.

Patients with sickle cell disease have blood cells that are stiff and misshapen. The cells dont carry oxygen as well and clog up the bloodstream, resulting in periodic bouts of excruciating pain.

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Patients with sickle cell disease have blood cells that are stiff and misshapen. The cells dont carry oxygen as well and clog up the bloodstream, resulting in periodic bouts of excruciating pain.

Ed Reschke/Getty Images

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 its supposed to, Frangoul says.

Then on July 2, after extracting Grays 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 wont cure sickle cell. But the hope is that the fetal hemoglobin will prevent many of the diseases 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.

Gray was diagnosed with sickle cell disease as an infant. She was considering a bone marrow transplant when she heard about the CRISPR study and jumped at the chance to volunteer.

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Gray was diagnosed with sickle cell disease as an infant. She was considering a bone marrow transplant when she heard about the CRISPR study and jumped at the chance to volunteer.

Meredith Rizzo/NPR

Concerns about risk

Other doctors and scientists are excited about the research. But theyre 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.

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Sickle Cell Therapy With CRISPR Gene Editing Shows Promise : Shots - Invest Records

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