A Patient Hopes Gene-Editing Can Help With Pain Of Sickle Cell Disease

Oct 10, 2019
Originally published on October 10, 2019 8:02 pm

Victoria Gray slides open a closet door, pulls out a suitcase and starts packing piles of clothes.

"My goodness," says Gray. "Did I really bring all this?"

Gray, who has sickle cell disease, is the first patient with a genetic disorder whom doctors in the United States have tried to treat using the powerful gene-editing technique CRISPR.

Today, Gray is getting ready to finally go home to Forest, Miss., after months away from her four children so she could undergo the experimental treatment, which involves infusions of genetically modified bone marrow cells.

"I'm very excited," says Gray, who has been living in a temporary apartment in Nashville, Tenn., for several weeks since getting discharged from the nearby TriStar Centennial Medical Center. "I know it's going to be emotional for me. I miss the hugs and the kisses and just everything."

NPR has exclusive access to chronicle Gray's journey through the highly anticipated clinical trial.

"Victoria is a pioneer in this. And we are very excited," says her doctor, Haydar Frangoul.

"I feel hopeful for the future," Gray says.

As a baby, Gray was diagnosed with sickle cell disease, which causes bouts of excruciating pain.
Meredith Rizzo/NPR

Sickle cell disease is a devastating genetic disease that afflicts millions of people around the world, including about 100,000 in the United States.

The disease is caused by a genetic defect that turns red blood cells into hard, sticky, sickle-shaped cells that don't carry oxygen well, clog the bloodstream, damage organs and cause torturous bouts of pain.

"The pain is excruciating. It's like being in a car accident and having lightning in your chest. It's a pain that makes a grown woman like me scream," Gray says. "It's an overwhelming pain."

Like many sickle cell patients, Victoria had to drop out of school, quit work and spend weeks in the hospital away from her family. Since many sickle cell patients don't survive past their 40s, Gray worries whether she'll live to see her children grow up. She just turned 34.

"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," Gray says. "Who wouldn't worry?"

But Gray has hope now, because in July doctors infused billions of her own bone marrow cells back into her body, after editing them with CRISPR.

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

Scientists used CRISPR to modify a gene in the cells to make them produce fetal hemoglobin, a protein that babies usually stop making shortly after birth. The hope is that the protein produced through the gene-editing treatment will give sickle cell patients like Gray healthy red blood cells.

CRISPR enables scientists to make very precise changes in DNA, raising hopes that the technique will lead to new ways to prevent and treat many diseases.

The sickle cell study is part of a wave of studies that are moving CRISPR out of the lab and into the clinic.

The two companies sponsoring the sickle cell study announced this year that they had used CRISPR to treat the first patient with a similar blood disorder, beta thalassemia, in Germany.

In July, one of the companies revealed the first hint that the approach might be working, at least in beta thalassemia: The patient's edited cells started functioning in the bone marrow, the company reported.

Doctors are also trying to use CRISPR to treat cancer. Most of those studies are underway in China. But three patients have been treated for cancer in a CRISPR study at the University of Pennsylvania in Philadelphia, and another study recently started recruiting cancer patients in the U.S. and Australia.

Complications from sickle cell disease caused Gray to drop out of school and quit work. She jumped at the chance to be part of the study at HCA Healthcare's Sarah Cannon Research Institute and TriStar Centennial Medical Center in Nashville, one of eight sites recruiting patients for the research in the U.S., Canada and Europe.
Meredith Rizzo/NPR

Later this year, doctors in Boston are planning to use CRISPR to edit cells in patients' retinas in hopes of restoring vision in patients with an inherited form of blindness.

Gray calls her 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," Gray says.

She adds with a laugh: "I'm just genetically modified now. I'm a GMO. Isn't that what they call it?"

Before Gray heads home, she has to see Frangoul, medical director of pediatric hematology/oncology at HCA Healthcare's Sarah Cannon Research Institute and TriStar Centennial Medical Center in Nashville.

Dr. Haydar Frangoul, medical director of pediatric hematology/oncology at HCA Healthcare's Sarah Cannon Research Institute and TriStar Centennial Medical Center, is leading the study in Nashville.
Meredith Rizzo/NPR

"This is a big moment for Victoria and for this pivotal trial. Because if we can show that this therapy is safe and effective, it can potentially change the lives of many patients," Frangoul says.

The study is being conducted jointly by Vertex Pharmaceuticals, in Boston, and CRISPR Therapeutics, in Cambridge, Mass.

Frangoul's site is one of eight recruiting patients in the U.S., Canada and Europe. Up to 45 patients ages 18 to 35 will eventually be enrolled.

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

Left: Before Gray can go home to Mississippi, she waits for another procedure to remove a port in her chest. Right: She is on a regimen of medications as part of her follow-up care. Frangoul will monitor Gray for years to determine whether there are any side effects from the CRISPR treatment.
Meredith Rizzo/NPR

So today nurses take 15 vials of blood from Gray as part of the testing to determine whether her edited cells are producing enough fetal hemoglobin to help her. She will return to the hospital once a month for four months for similar blood tests as well as a bone marrow biopsy.

Gray will also keep a detailed diary to track her health, including how much pain she is experiencing, how much pain medication she needs, whether she needs blood transfusions and whether she experiences any complications from sickle cell disease. The hope is that the treatment will reduce the severity of her disease's symptoms.

In addition, Frangoul will monitor Gray for years to check for any signs of side effects from the treatment itself.

Registered nurses Bonnie Carroll (left) and Brooke Ryan draw blood from Gray.
Meredith Rizzo/NPR

"My hope and dream for Victoria is to allow her to spend quality time with her family — go to the park with them, play with them — without having to struggle with pain and weakness," Frangoul says.

"I would love Victoria to be able to live a healthy, normal life. And she can see her — not only her children's graduation from high school but from colleges and getting married and having grandkids," he says.

Victoria hopes so too.

"Not just for me but for other people. This would be mind-blowing," Gray says. "I can't imagine the lives that could be saved if this thing actually works. Yeah, oh my God. Just to not have to deal with that pain anymore is enough."

She knows it's unclear when she will know whether it's working.

"I try not to focus on dates and when I'm going to find this out, because I don't want to stress," Gray says. "So I think about just looking forward to the future and just see what comes of it. I've done it. So the hardest part is over. So now it's just waiting."

Copyright 2019 NPR. To see more, visit https://www.npr.org.
Although Gray will finally go home to Forest, Miss., she will return to Nashville once a month for four months to undergo blood tests and a bone marrow biopsy. But, she says, the hardest part is over.
Meredith Rizzo/NPR

STEVE INSKEEP, HOST:

OK. The first person to get treated in one of the most closely watched medical experiments in decades is now waiting - waiting to learn if the treatment is working. NPR health correspondent Rob Stein introduced us to Victoria Gray this summer. And now he continues his exclusive look at her story.

(SOUNDBITE OF KNOCKING)

ROB STEIN, BYLINE: Hi. Good to see you.

VICTORIA GRAY: Good to see you, too.

STEIN: I catch up with Victoria Gray in an apartment in Nashville near the hospital where she volunteered for the first attempt to use the revolutionary gene-editing technique called CRISPR to treat a genetic disease in the United States.

Thank you so much for seeing us and letting us come over. I really appreciate it.

GRAY: No problem.

STEIN: Victoria's packing. She's finally going home tomorrow to see her four kids in Mississippi for the first time in months.

GRAY: I'm excited, you know. I'm very excited about it. I know it's going to be emotional for me. I miss the hugs and the kisses and - just everything.

STEIN: You must be so excited.

GRAY: Yes, I am (laughter). Yes, I am.

(SOUNDBITE OF ZIPPER UNZIPPING)

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

GRAY: Oh, my goodness. Did I really bring all of this?

STEIN: Victoria has sickle cell disease, a terrible genetic disorder that turns her red blood cells into deformed sickle-shaped cells that clog her bloodstream, ravage her body and torture her with agonizing bouts of pain.

GRAY: The pain is excruciating. It's like being in a car accident and having lightning in your chest. It's pain that makes a grown woman like me scream.

STEIN: Oh, my God. That just sounds terrible.

GRAY: Yeah. It's a overwhelming pain.

STEIN: Like many sickle cell patients, Victoria had to drop out of school, quit work, spend weeks in the hospital away from her kids, worry whether she'll live to see them grow up.

GRAY: It's horrible.

STEIN: You have to live with that every day.

GRAY: Yes - knowing that I could have a stroke or a heart attack at any time because I have these cells in me that are misshapen. Who wouldn't worry?

STEIN: But now Victoria has hope because doctors infused billions of her own cells back into her body this summer, cells Victoria calls her...

GRAY: Super cells.

STEIN: ...Because scientists altered a gene in the cells with CRISPR, which makes rewriting DNA really easy, to hopefully give Victoria normal, healthy red blood cells.

GRAY: Super cells. Yes. Yes. They got to be super, do great things in my body, you know, and to help me be better, you know, and help me have more time with my kids and my family.

(SOUNDBITE OF ZIPPER ZIPPING)

GRAY: That's one.

STEIN: First suitcase done?

GRAY: Yes (laughter).

STEIN: But before Victoria can finish packing and go home, she has to stop by the TriStar Centennial Medical Center in Nashville again.

HAYDAR FRANGOUL: So how have you been doing?

GRAY: I'm doing good.

FRANGOUL: So, yeah, this is a big moment, friend.

GRAY: Yes.

STEIN: Dr. Haydar Frangoul at the Sarah Cannon Research Institute treated Victoria.

FRANGOUL: Are you excited about seeing the kids?

GRAY: Yes, I am.

FRANGOUL: Are they going to have a big welcome sign for you in Mississippi?

GRAY: No because it's a surprise.

FRANGOUL: Oh, you didn't tell them?

GRAY: No one knows I'm coming.

FRANGOUL: You did not tell them?

GRAY: No.

FRANGOUL: Oh, wow. So they don't know you are coming?

GRAY: No. No. No. I'm just going to show up tomorrow, like, Momma's home (laughter).

FRANGOUL: That's pretty good. OK. Let's check you out.

GRAY: OK.

FRANGOUL: Take a deep breath for me.

STEIN: Dr. Frangoul says Victoria will come back once a month for checkups and blood tests to see if her super cells are producing something called fetal hemoglobin.

FRANGOUL: We are very hopeful that this will work for Victoria, but we don't know that yet.

STEIN: So Victoria will also keep detailed diaries about her health, how much pain she's having, how much pain medication she needs, blood transfusions.

FRANGOUL: Victoria is a pioneer in this. We are very excited. This is a big moment for Victoria and for this pivotal trial because if we can show that this therapy is safe and effective, it can potentially change the lives of many patients.

STEIN: Dr. Frangoul will also watch over Victoria for years to see if the treatment is preventing organ damage, heart attacks, strokes and other complications that takes the lives of sickle cell patients and for any signs of any side effects from the treatment.

FRANGOUL: My hope and dream for Victoria is to allow her to spend quality time with her family, go to the park with them, play with them without having to struggle with pain and weakness. I would love Victoria to be able to live a healthy, normal life. And she can see her - not only her children's graduation from high school but from colleges and getting married and having grandkids.

STEIN: Victoria hope so, too.

GRAY: Not just for me, but for other people, this would be mind-blowing. And, oh, my God, I can't imagine, you know, the lives that could be saved if this thing actually worked.

STEIN: That would be amazing.

GRAY: Yes, it would be.

(SOUNDBITE OF CURTAINS OPENING)

STEIN: Now it's time for the nurses to get some of Victoria's blood for the study she's in. It's being conducted by two biotech companies and will eventually involve dozens of patients in the United States, Canada and Europe.

UNIDENTIFIED PERSON: All right. So how many days have you been here?

GRAY: I think we're in, like, day 80.

UNIDENTIFIED PERSON: Oh, I can't believe you're really leaving.

STEIN: As nurses Bonnie Carroll and Brooke Ryan fill one big vial after another, I realize I never asked Victoria something.

Is it weird to have genetically-modified cells in your body?

GRAY: No. I'm just genetically-modified now (laughter). I'm a GMO. Is that what they call it?

STEIN: Finally the nurses are done. And it's time to say goodbye for now.

UNIDENTIFIED PERSON: Good job. You did it.

GRAY: Thank y'all. Y'all going to make me cry.

(LAUGHTER)

UNIDENTIFIED PERSON: No (laughter). You're fine.

STEIN: But before I say goodbye to Victoria, I asked her about what comes next - this limbo period, waiting to find out if her super cells are working.

GRAY: Well, I'm spiritual, Rob. And it's something I prayed about. And just the way everything happened for me, I just feel like it was fate for me to be here. I just believe that, you know, God is doing this for me. You know, that's all I can say. So yes, pray (laughter).

STEIN: Rob Stein, NPR News, Nashville.

(SOUNDBITE OF ARMS AND SLEEPERS' "WHEN THE BODY") Transcript provided by NPR, Copyright NPR.