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Warrior Spirit: An Interview with Victoria Gray, Sickle Cell Pioneer

2024; Mary Ann Liebert, Inc.; Volume: 7; Issue: 1 Linguagem: Inglês

10.1089/crispr.2024.29171.vgr

2573-1602

Victoria Gray, Uduak Thomas, Kevin Davies,

CRISPR and Genetic Engineering

The CRISPR JournalVol. 7, No. 1 InterviewFree AccessWarrior Spirit: An Interview with Victoria Gray, Sickle Cell PioneerVictoria Gray, Uduak Thomas, and Kevin DaviesVictoria GrayForest, Mississippi, USA.Search for more papers by this author, Uduak ThomasSenior Editor, Genetic Engineering & Biotechnology News.Search for more papers by this author, and Kevin Davies*Address correspondence to: Kevin Davies, Executive Editor, The CRISPR Journal. E-mail Address: [email protected]Executive Editor, The CRISPR Journal.Search for more papers by this authorPublished Online:14 Feb 2024https://doi.org/10.1089/crispr.2024.29171.vgrAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookXLinked InRedditEmail Victoria Gray.(Photo credit: Kenyon Blanden Photography.)In July 2019, medical staff in Nashville dosed the first U.S. patient in the exa-cel therapy trial, sponsored by Vertex Pharmaceuticals and CRISPR Therapeutics. That first patient was Victoria Gray, a mother of four from Forest, Mississippi, a sickle cell warrior and a true pioneer in the world of CRISPR and cell therapy. That process began 4.5 years ago. Today, she is healthy, enjoying a pain-free life with her family and friends—as are dozens of other sickle cell patients who participated in the trial. In December 2023, the U.S. Food and Drug Administration (FDA) approved Casgevy, setting a list price of $2.2 million for the one-time therapy.In January 2024, Executive Editor Kevin Davies and GEN Senior Editor Uduak Thomas interviewed Gray for "The State of Cell and Gene Therapy," a GEN virtual summit that was broadcast on January 24, 2024.(This interview has been lightly edited for length and clarity.)Victoria, how are you feeling today?Gray: I'm still doing good—way better than I expected in the beginning. So life is good for me right now.What can you do now today with your family that you were not able to for your entire life?Gray: Up until that point, I couldn't do anything that calls for exertion—exercise, walking for long periods of time. It was hard for me to keep up with my young kids. When they asked me to jump on the trampoline with them, I could only last 5 s before I had to get off, which wasn't fine for them, neither for me! So just the basics I had trouble doing. especially toward the end.About 5 years before the [exa-cel] gene therapy, I was homebound, so I had to have someone in my house to help me get in the bath to dress, comb my hair. I don't need that anymore. I do all those things myself. I get to be a regular mom, wife, human being!You call your gene-edited cells your "supercells"—do they still have their superpowers?Gray: Yes, because they went from the cells that were causing me all kinds of pain, strife, depression, now to the healthy cells that give me energy, make me happy, and are going to help me live longer to be here for my children.In December 2023, you went back to see your physician, Dr Haydar Frangoul in Nashville. What did that post-4-year checkup entail?Gray: Yes. It was only blood work and my labs, and to see if I was still producing fetal hemoglobin. Everything checked out.Your story has been told over the past 4 years on National Public Radio. You have achieved a certain level of celebrity. Is that a role that you are enjoying?Gray: Yes, I am embracing it because I feel before that I didn't have a voice with sickle cell disease (SCD). And I felt like sickle cell patients didn't really have a voice. There were many times I complained as a patient and nothing was done. So now I have this opportunity to be a voice, not just for myself, but also for other sickle cell patients who are still suffering. I feel this is my purpose. There are other little girls and boys, like me, suffering and feeling voiceless.Let us go back to your childhood in Mississippi. When were you first diagnosed?Gray: My diagnosis came at 3 months. They did the newborn screening but my mom didn't hear anything about the screening or about the results until I had my first crisis at 3 months. She was giving me a bath. I started to cry, and she assumed that it was from my shoulder because the doctors dislocated it during my birth. She took me to the emergency room, thinking it was just that, and they could make that better. But to hear that I had SCD, and that I may only be with her for 7 years, she was not prepared to hear that. From then on my childhood was riddled with unexpected episodes of pain and doctors' appointments, hospital visits, blood transfusions, and medications.Did you have any relatives or cousins with SCD in the family?Gray: It was a surprise. I found out later that I had an older distant cousin who had sickle cell, so we had no connections. We hadn't met each other or anything, so that made me feel isolated, not knowing anyone else who had SCD. My brothers and sisters were just fine, and I couldn't keep up.How was it explained to you? It is not a physical disease where you can see something happening on your skin or running a fever.Gray: I remember not my family explaining it but my hematologists. I had three hematologists as a kid, so I saw the same doctors then. Drs Smith, Iyer, and Pullen explained that my blood cells were supposed to be round, and sometimes their shape changes and they become sharp and sticky. That's why I hurt and that's what makes me feel bad. I didn't really understand everything, but I used to love to read. I started reading about sickle cell myself. To read that yourself as a kid, especially in the early '90s, it is devastating. So I stopped looking it up because I saw death.I remember as early as preschool, having a sickle cell crisis after school and not being able to go outside and play with my friend Candies, and my grandmother having to get my cousin to drive me to Jackson, Mississippi. The hospital was an hour away from our home… Even when I went to my regular appointments, if my blood counts were low that day, I got transfused. That day I was able to go home but I had to stay for a few hours to get blood transfusions, so it was all I knew.It sounds like you learned early on what some of the triggers were—exercise, maybe stress. Were there other things that would lead to a pain crisis?Gray: Changes in weather, if I got too cold… I felt like just living itself was a trigger, because I couldn't control the weather. I couldn't control stress because things come every day unexpectedly, and I was a child. Of course, I'm going to test my limits and go out and climb this tree with my brother!What did a pain crisis feel like to you?Gray: Imagine getting struck by lightning. You're having a normal day and then this pain is flowing from one arm to the other, and your bones feel as though they have been crushed as if you got hit by a car. Your bones are aching and they have these sharp electric-type pains just running all over your body. It's not in one place. My hand is hurting, my arm, my legs, my chest.So when my doctor asked what was wrong, I just said everything 'cause I felt pain everywhere blood was supposed to flow. But I had these blockages, so it was causing me pain and fatigue, it was a horrible experience.They would suggest hot towels, massages—my grandmother tried all of it, but the touching and rubbing it would not touch my pain, because the pain was so deep. It could go on for weeks at a time. You never know when it was going to start and, worst of all, you never know when it was going to end. It was different every time.Did you take hydroxyurea at all? Was that helpful?Gray: Yes, I began taking hydroxyurea as a teenager. I didn't see some of the effects that other patients were seeing. I thought it was just me. As I researched it, I came across a sister and brother online on a commercial. She spoke about how she benefited and didn't have to get hospitalized. But her brother didn't get the same benefits. It didn't work for me.You went to college and had plans to study nursing. What made you want to study nursing?Gray: I know you think you can guess. But as of the first day of college I was going to be a cardiologist, because my grandmother had a heart condition. So it wasn't about sickle cell at all. I was doing it to help other people. I was thinking about my mom—because that's what I called her—but when I saw the list, and how long I would have to be in school, I felt I couldn't accomplish it, because I was sick more and more. Nursing was actually option number 2. I was like, if I can't be a doctor, I'll be a nurse. So I started pursuing my nursing degree. But my health got worse. I had done all my prerequisites. And I had taken the test to get into the nursing program. But I couldn't start it.Did your condition give you pause before starting a family with your husband?Gray: I always knew I wanted kids. So when it became time, when I felt I was ready, I got my partner tested. My hematologist offered to test him for free, because I knew [my children] would automatically get the trait from me. I felt that if their dad didn't have the trait at all, my kids would be safe. So I did the testing. He didn't have sickle cell trait so it was a green light for me.My pregnancies went better than I expected, because being a sickle cell patient, you are high risk. The cells can pile up and cause your baby to lose oxygen, and you can have all kinds of complications. I prayed, because I wanted these children, and I know God could give me the desires of my heart. I did have a crisis during my pregnancy, but it didn't affect my children, and it wasn't as bad as the ones that I was having when I wasn't pregnant. I'm blessed!How did you talk to your children about the disease as they got older?Gray: I didn't even wait until they got older. I started having smaller conversations with them when they were younger, because I didn't want them to be confused to why I was in the hospital, how they could go to bed? I put them to bed, and they wake up and I'm not there anymore. I explained to them that mama gets sick, that I have SCD. It causes me to get tired, to hurt, and I have to go to the hospital to feel better. So they understood that part. Even around ages 8 or 9 years, I explained to them that they had sickle cell trait, and that there's a possibility that they could pass that on. I want them to be educated and knowledgeable, because I know there is the chance they grow up and meet someone who had sickle cell trait. And then they have to experience the horrors of sickle cell all over again.It sounds like your faith has been an important part of helping you in your life thus far?Gray: Yes, it has been. My grandmother took me to church all the time. She would pray out loud. I knew the power of Jesus Christ growing up. It can be a little confusing at times, so I had to make it personal and ask God to show me his strength. There have been other circumstances in my life where I knew it was real to me. I haven't been let down. I've been through a lot and I've had a lot of close calls with death. But God saw me through it.At one point you were considering a bone marrow transplant. Who was the donor going to be and how far did you go along that path?Gray: Yes, I had heard about bone marrow transplants in the paper. The hospitals here [in Mississippi] didn't know about the [haplo-identical] transplant I would need, because I didn't have a 100% match within my family. Dr Frangoul reached out to my hematologist asking whether she had any patients who would consider bone marrow transplant. She thought of me because I had been feeling low and hopeless for the past few months, so she was excited to share that news.I traveled to Nashville, Tennessee, with my husband and my older brother Timothy, in hopes of getting a bone marrow transplant, and him being my donor. I knew he would be my closest match. When I went there, I was depressed, looking and hoping, but not having my hopes up too high, because I wasn't sure yet if my brother was a match. We met with Dr. Frangoul in March 2018. We did laboratory work to see whether he was a match, and he was a match to be my donor. He was a half match, though.We went about 6 months, pursuing the transplant with my brother back and forth with testing. I was in Nashville preparing to do another test. But I had a sickle cell crisis. During the hospital stay, Dr. Frangoul knew of my fear of graft versus host disease. That was one of the things that I was afraid of contracting with the bone marrow transplant. He said at my bedside, "Victoria, we have this new study coming up, and it's CRISPR. Have you heard of it?" Of course, I hadn't. He explained how the edit would take place. He said, "But you'll be the first person to try it!"Making a Statement: Vertex Pharmaceuticals, headquartered in Boston's Seaport neighborhood, won approval for Casgevy, the CRISPR-based cell therapy for sickle cell disease, in December 2023. Approval for beta thalassemia followed in January 2024. Photo credit: (Vertex Pharmaceuticals.)I took a breath and said, "Well, I have two questions. If it doesn't work, can I do the transplant with my brother? And is there a chance of graph vs host disease?" When he told me there was no chance of graft vs host disease, because I will be receiving my own cells, and then, if it didn't work, I could do the transplant with my brother within the next year. It was a yes from me!You had to put a lot of faith in Dr. Frangoul as well?Gray: From the day I first met him in March 2018, [I liked] his demeanor, his personality. It was uplifting. It was something that I hadn't experienced in years since I left pediatric care. So it was refreshing, and when I spoke to him about my pain and what I had been going through, he was able to empathize, he wanted to help me. It seemed genuine, from his infectious laugh and his personality. I felt faith with Dr. Frangoul, because I really felt that he had my best interests in mind.Once I was discharged from the hospital and came home, I prayed about it. I asked God, "If this is for me and my gateway to my miracle, remove all fears that I may have. Help me to go in it with an open mind, open heart, and fearless." So I did it just that way.Future sickle cell patients will go through this process now that Casgevy is approved. Can you walk us through the steps?Gray: It was a long testing phase! I had to get my lungs, my heart, my liver, everything tested, and I also had to go on an apheresis plan where they would remove my blood with a machine every 3–4 weeks and replace it with healthy red blood cells, just to keep my body healthier and to keep me from having so many crises while I wait. Then I had to get admitted to the hospital. They gave me a shot in the back of my arm to release my stem cells out of my bone marrow into my blood flow to be collected. Then I had to get on another apheresis machine for hours where it pulled my blood out, spin it, and collect the stem cells. So I did that on 2 separate days to where they felt like they had enough to transport it to the laboratory and receive the edit.It took a few months for my cells be ready after they done the edit. Once they were ready, I got admitted to the hospital, June 25, 2019. I had to go through 2 to 3 rounds of chemotherapy, like 2 to 3 days of chemotherapy. Then I had 2 days of rest. After the rest day I received my new cells. It was three syringes. They pushed it through the same port that I had in my chest, that I had received my blood transfusions and my medications through. It seemed so simple! That's it? He just pushed the needle in. I was so overwhelmed with joy that day, because I felt like my life was changing, that I was done with the suffering side of sickle cell, it wouldn't have a hold on me anymore.That was good, those days of chemo and receiving the new cells—easy, peasy!! But 2 weeks later, the side effects of the chemo drug started to kick in. That was a whole different story. Nothing easy about it. I lost my hair. I was prepared for that. Me and my dad laughed about it because he's naturally bald now! The next day I started to get sores in my mouth, that Dr. Frangoul had said would come as a side effect of the Busulfan. It was in my mouth and in my throat. It was so painful it hurt to swallow just my saliva. I cried, I wasn't used to it. I had to do suction, I couldn't eat. They gave me nutrients through my IV that lasted for about 2 weeks. That was my toughest point. Of course I was weak, but I couldn't tell the difference between whether I was weak from the chemo or the weakness that I have experienced for years with my SCD.But with Doctor Frangoul's upbeat spirit… He would come in the room every morning, and said, "Victoria, you should be bouncing off the walls by now, girl!" I started to time him on when he would come in the mornings, try to have my bath, and be up and out of bed with my makeup on at least so he can know I'm moving around, doing something. I began to walk the halls. I was in isolation in a pediatric ward. Being around those kids, who were so full of energy, even though they were going through different problems with cancer. They gave me hope, hearing them ride their electric cars in the hallway reminded me of my babies back home. I was surrounded pretty much by light doing that experience, which made it easier.When did you get the sense that the procedure had worked?Gray: We expected that I would have to get transfused multiple times after the procedure. I only got one transfusion. Dr Frangoul said, "Wow, your numbers are doing good, girl!" I was happy because I'm also afraid of blood transfusion, because you have to sign a waiver, and it's a chance for a reaction. So I don't like having to get them, even though I've been getting them since my childhood. It still scared me.I didn't have to get the extra blood transfusion and platelets as expected, and I wasn't having any vomiting or high fevers. I didn't get any infections, so they were all good signs. But even once I got discharged, I had to stay in Nashville for 2.5 months. Thirty days I was in the hospital, but the rest of the time I was in the apartment less than 5 min away from the hospital, just in case something went wrong.I didn't have any "just in case" moments. So I went home early. I still did well at home. I didn't have to go to the emergency room. My pain, I still had aches but they were managed with my medications, which was unusualWhen we made it to 6 months, that that was new for me, because the past few years I hadn't been able to make it 6 months without a crisis or being in the emergency room. So I asked Dr. Frangoul to taper me off the fentanyl and Dilaudid I'd been taking because how could I be sure that I'm better if I'm still on all these medications? So we began to taper. I did well until I couldn't get the medicine for the taper because of the COVID-19 shutdown—it was hard to come into the pharmacy, so I had to go cold turkey for a while.That was horrible, that sent me into flu like symptoms. I was irritable, aching, nose running. I was miserable during that phase, and there was a lot going on in the world at the time—my husband was deployed. I was at home with the kids trying to navigate COVID-19, virtual school, then we had the racial stuff going on. It was a hard period.But I recovered. Dr Frangoul was able to ship me some methadone. Once I got through that phase, it was about 8 months total after coming home. I woke up one morning and I didn't feel anything. I was scared. I was afraid. So I started to pinch my face, my thighs. I had to call my kids in the room this early morning, so I called them to come in, so I was like, if they can see me. I can see them. They can touch me. I'm alive. So they came like, hey, mom, I was like, oh, I just wanna see y'all, come give mama a hug. Good morning. And they went on back their way. And then that's when he hit me: "Vicky, you're better."I said, "Lord, I thank you," because that was my first morning waking up, not feeling stiff, not hurting. Nothing was going on! I felt so light, I thought I wasn't even alive. It was a brand new feeling and a brand new day after that.In March 2023, you took your first overseas flight to London to share your story at the International Human Genome Editing Conference. What was that experience like?Gray: The experience was great! I enjoyed the flight, even though it was long, but the whole time I was thinking like, wow, I would have never been able to do this before. I was able to tour London and walk for hours. It was just amazing to see this, this new place, all the people, and we went to different museums and the artwork. The experience blew my mind!You were there to give a presentation. Were you nervous walking up onto that stage?Gray: Yes, I was very nervous. This was my first time on a big stage with a platform and an international audience from everywhere! But I felt like in that moment, I was fulfilling my purpose and my promise to God. Because I did say, doing all those prayers to God, "If you do this for me, I would tell the world about it." At the time I was thinking the church, my small community here in Forest. But to be given the opportunity to be in front of the world because it was people from Africa, India, Asia, the islands, everywhere. I was like, okay, really making me fulfill this promise?!After the approval of Casgevy [on December 8, 2023], you posted your reaction on Linkedin.Gray: I told my husband when I woke up that morning, "They're supposed to make the decision today, but I have to work. Let me know when the decision comes." So I was at work, and he sent me a text message, and he just said, they approved it.It was time for my lunch break. I started shaking automatically, cause. I was so excited and thrilled, and I had to immediately leave work, and go to my car. I was crying! I didn't expect to have that overwhelming reaction. I was hoping and praying, and I felt that they would pass it. But I want to just say, oh, this is going to happen and get let down. So when it happened, it brought back all the raw emotions. I started to feel and think about all my hospital stays when I thought I wouldn't make it, and the suffering and feeling alone, the depression I went through.And to think that this therapy is here for the ones who are in that phase right now, who are going to be able to get help and feel understood, feel heard? Because I thought sickle cell wouldn't get this type of treatment ever. I really felt—I can be honest—who cares about us?I've never seen a sickle cell commercial. I felt no one cared, and there was no real help coming. So that day was monumental for me. I was just overwhelmed with joy.The list price of Casgevy is $2.2 million. What's your reaction to that?Gray: That price? Oh, my goodness! I would never have been able to afford it even with me, working full time now. So I think and I pray that insurance companies would decide to take up that cost. So people who actually need it can get it. If not, it would just be sitting on the shelf collecting dust, pretty much, because most people with SCD can't work full time. I was homebound and that's a huge burden to place on a family who's already burdened, for the mother or dad or cousins to try to figure out how to come up with $2.2 million. It takes some of the joy that you feel when you hear. Oh, this is a new thing! Who can give me a new chance at life. And then you hear $2.2 million, and like, this is not going to happen for me.I believe in us, in people. I feel like we should work together to cover this cost—some way. Somehow. I'm not a numbers person. I don't know anything about how to get that done. I hope the ones who do know how to make this work will figure it out.How would you advise SCD patients who are interested in this new cell therapy?Gray: I have spoken to people before they decided to sign up for the trial evenly. I'd get them to just take a look at everything they've already encountered the pain and having to go through the emergency room and deal with doctors and nurses who don't believe that you're really hurting because we look like this, and we go in sometimes calm, because we've experienced pain for years, but they [concluded], "You're not hurting, you must be looking for drugs." I had to start taking my Dilaudid prescription in my purse with 4 mg to show them, because they will want to give me 1 mg Dilaudid. I was like, "Look, I have 4 mg in my purse that I'm taking and it's not helping."I let them understand that this is a personal decision, of course, I don't try to force it on anyone, but I can speak about my own outcome, and that it was worth it to me, because now I don't have to go to the hospitals anymore or get about a bed in the middle of the night. I get to work and make my own money. You hear that you have to be in the hospital for 30 days, but before treatment. I had a crisis that put me in the hospital for 3 months. So 30 days was nothing to me!For patients with younger kids. I explained that when I was young, I didn't have as many crises. My crises got worse and more frequent with age, and when you're older you're going to have more stress trying to navigate the world, so it may seem like twice a year right now is no big deal. But if you can prevent going from twice a year to once a month, and possibly every other week in the hospital, is it worth it? So the actual question that I ask them is, do they think it's worth it? You have to go into a procedure like this with a positive mind and positive attitude, because it is a rough one.What are your hopes for the future?Gray: I want to do more public speaking. I want to write a book and tell my story in detail, because there's a lot that needs to be told. I want to counsel and meet as many sickle cell patients as I can, to be a patient advocate to see whether we can get this job done to get this price to come down or have our insurance coverage. To do what we need to do and be a voice.And I pray that one day I would be in a position to bless someone to get this procedure. I'm not there financially yet, but I would love to say, "Hey, I'm going to give this to you because it's a great gift."FiguresReferencesRelatedDetails Volume 7Issue 1Feb 2024 InformationCopyright 2024, Mary Ann Liebert, Inc., publishersTo cite this article:Victoria Gray, Uduak Thomas, and Kevin Davies.Warrior Spirit: An Interview with Victoria Gray, Sickle Cell Pioneer.The CRISPR Journal.Feb 2024.5-11.http://doi.org/10.1089/crispr.2024.29171.vgrPublished in Volume: 7 Issue 1: February 14, 2024 PDF download