September 12, 2024
This article originally appeared in AABB News, a benefit of AABB membership. Join AABB today to read the rest of this month’s issue.
Victoria Gray, 39, experienced her first sickle cell crisis at three months old. An emergency room visit led to an unexpected sickle cell disease (SCD) diagnosis. Doctors gave her mother a grim prognosis—a life expectancy of up to seven years.
“My mother initially thought I was inconsolable because my shoulder dislocated during my birth. But after the testing and the doctor’s report, she thought I was going to die,” Gray said. “Coming from a family of faith, my grandmother encouraged her to trust God. I took on that mentality throughout my entire life.”
For Gray, growing up with SCD was a constant uphill battle. She endured frequent sickle cell crises, the unrelenting pain shooting across her chest and arms like lightening at any given moment. These debilitating episodes kept her home from school for weeks at a time. Emergency room visits for pain management and blood transfusions became a regular part of her childhood.
“You never knew when the pain was going to start. It was very taxing as a kid,” Gray stated. “There were many things I dreamed about doing, like cheerleading and playing basketball, but my doctor always told me I couldn’t because of SCD. I signed up for the United States Navy in my senior year, but I was denied.”
Gray noted the frequency and severity of her sickle cell crises increased as an adult, and she began losing hope during her most memorable crisis in 2010. The painful episode left her bedridden and hospitalized for three months. Gray, who lost her ability to walk, bathe and feed herself, said her frequent hospitalizations and limited mobility chipped away at her confidence as a wife and mother to her four children.
“I missed all my children’s birthdays and Thanksgiving and Christmas with my family. I was fighting to be here. I even gave up on my nursing dream to focus on my family, but even that became a challenge because I was always in the hospital. I was getting blood transfusions monthly to prevent a crisis, but it didn’t work,” Gray said. “I just felt like I wasn’t being a good mom. I couldn’t do the things other mothers could do. I couldn’t show up for my husband during his deployments or travel like the other military wives. SCD made everything tough, and I wanted to give up. I wasn’t adding to anyone’s life, and my life wasn’t worth living anymore. I was just existing.”
Gray knew something had to change when she learned her oldest son was acting out at school because he feared she would pass away while he was in class.
“He wanted to get kicked out so he could watch me at home,” she noted. “That’s when I started researching available treatment options for SCD and learned about haploidentical bone marrow transplants. It gave me hope while I faced another severe sickle cell crisis. My doctors didn’t have any answers or solutions for me. I kept researching and I prayed to God for a solution that would allow me to live long enough to see my children grow up.”
Gray noted her faith kept her grounded throughout her journey with SCD and credited her grandmother for instilling spiritual values in her as a child. Faith can help you face any diagnosis, she added.
“At one point it seemed like I was getting bad news every time I saw the doctor, but my faith helped me hold on and believe that God was going to see me through it and provide a way, no matter the doctor’s report,” Gray told AABB News.
In 2018, Gray, a resident of Forest, Miss., and her brother traveled to Nashville, Tenn., with high hopes of undergoing a bone marrow transplant. That’s when she learned about a groundbreaking clinical trial for SCD using gene-editing technology.
“I tried out for many medical trials before, but I never qualified because I was too ill to participate. When Dr. Haydar Frangoul approached my bedside during a crisis and told me about the CRISPR gene therapy trial, I was interested,” she said. Frangoul, medical director of pediatric hematology/oncology for the Sarah Cannon Pediatric Transplant and Cellular Therapy Program at TriStar Centennial in Nashville, explained the pros and cons of the experimental therapy—which had never been used on patients with SCD before. If gene therapy failed, he assured her she could still move forward with the bone marrow transplant.
“Pursuing this option also meant I wouldn’t have to worry about contracting graft-versus-host-disease (GVHD), which can occur after a bone marrow transplant,” Gray said. “That was my biggest fear. I didn’t want to trade the devil I knew— SCD—for a whole different beast. But knowing I would be the first was scary.”
After much thought and prayer, Gray volunteered for the trial and became the first patient to receive CRISPR gene therapy for SCD.
“My main confirmation was prayer. I gave my yes to be the first, not even knowing that it would become a big deal,” Gray said. “I knew what it would mean for sickle cell warriors if this gene therapy worked. Somebody had to be the first; why not me?”
CRISPR sickle cell gene therapy aims to repair the mutation in the adult hemoglobin gene responsible for SCD. The gene editing tool can be used to extract, correct and replace patients’ hematopoietic stem cells. The U.S. Food and Drug Administration (FDA) approved Casgevy, a CRISPR-based gene editing therapy, for the treatment of SCD on December 8, 2023. According to the FDA, CRISPR/Cas9 can be directed to cut DNA in targeted areas, enabling the ability to accurately edit DNA where it was cut. The modified blood stem cells are transplanted back into the patient where they engraft within the bone marrow and increase the production of fetal hemoglobin (HbF). The CRISPR-Cas9-edited blood stem cells are returned to the patient as a one-time, single-dose infusion. Before reinfusing the modified cells, the patient must undergo high-dose chemotherapy to remove affected cells from the bone marrow.
Gray described the treatment as a lengthy and arduous process that required extensive testing and frequent trips to Nashville for treatment over eight months. Her health care team this time around included a therapist to provide mental health support. The cell collection phase required her to be on a machine for six hours a day for three days to harvest her cells, followed by a month-long myeloablative conditioning phase that included intense chemotherapy. She cited oral mucositis as the most challenging side effect.
“The mouth and throat sores made eating so painful. Swallowing my own saliva felt like glass in my throat,” she explained.
On July 2, 2019, more than 2 billion of Gray’s newly edited CRISPR cells were reinfused into her body through a catheter in her chest.
“Dr. Frangoul injected my new cells through a large syringe with a single push and gave me a high five. I stared at him in disbelief. I just couldn’t believe it,” Gray said. “I cried that day because I was just so full of joy. The trial made me more hopeful because life had become dreadful. Although nothing had changed at that exact moment, I had faith and believed the therapy would work.”
After her release, Gray returned home to Mississippi with minor aches and pains. But as the weeks passed, she noticed her body’s red blood cell count did not drop to a critical level. To that end, she didn’t need a blood transfusion. Gray began to taper off her daily pain medication and eventually was able to quit altogether.
Gray recalled the moment everything changed. Eight months after her treatment, she woke up one morning feeling completely different: no pain, no soreness. She pinched her face and legs to make sure she was still breathing.
“The room was bright and quiet. At first, I thought I was dead. I called my kids to make sure they could see and hear me,” Gray said. “They rushed into the room, and I gave them a huge hug. That’s when I realized this is what normal feels like. It was the first day I had ever woken up in more than 30 years without any pain in my body. Things were different. And they continued to be different.”
The disease that had plagued Gray her entire life no longer limited her. She raced her boys in the yard and jumped on the trampoline without fatigue or pain. She watched her daughter dance in the Christmas parade, the cold temperatures no longer triggering a pain crisis. She took her first flight to Washington D.C., where her husband was stationed. She landed her first full-time job outside the home.
“I can contribute to my household and show up for my family,” Gray said. “I feel like I’m a part of society now. I had been isolated for years, but now I’m free to be me and dream again. I don’t have to give up my dreams because of pain anymore.”
Gray was overcome with emotion as she recounted the joy on her son’s face when she attended his football game.
“To see his face when he saw me in the football stands... He told his coach, ‘You got to put me in the game. My mama’s here,’” Gray recalled. “I’m just grateful to be present.”
Gray has not had a sickle cell crisis or blood transfusion since her treatment. She no longer takes any medication for SCD, and she remains symptom free. Life is different, Gray pointed out.
“I no longer have a fear of death,” she said. “There’s more to life now than just waking up and going to the hospital or doctor appointments and staying in bed. I’m not just existing anymore but thriving.”
As the first CRISPR gene therapy recipient for SCD, Gray has shared her experience with countless media outlets and travels as an international speaker. She said she wants her story to give other sickle cell warriors hope in the darkness. “When I was struggling, I felt like no one cared about my disease and help wasn’t coming for me. You start getting labeled as a drug seeker, and all the judgment coming from health care providers really sent me into a depression. The people who were supposed to help me didn’t understand,” Gray told AABB News.
“There is a big spotlight on SCD today that didn’t exist before. There are people working on behalf of warriors to relieve the pain and fears associated with this disease.”
Gray said her journey has led to her purpose, providing her with a platform to advocate for sickle cell warriors and tell others about CRISPR.
“I encourage warriors not to give up. Even if this particular gene therapy is not for them, I want them to hold on because other treatments are coming,” Gray said. “I always thought SCD was going to be my beginning and end. This has all been unexpected, but it was a part of God’s plan. This therapy has opened the door to a whole new treatment for SCD. It’s an amazing feeling to be the first, but I remain humble. I don’t feel famous. I’m just Victoria. A sickle cell warrior who wanted to be here for her children and her husband.”
*Learn more about Victoria Gray's story of resilience during her AABB Instagram takeover on Monday, Sept. 30. During the takeover, Gray will bring followers along as she shares her experience as someone who lived with SCD and highlights the transformative power of gene therapy. AABB encourages members of the blood and biotherapies community to follow the takeover using the #AABBscd Instagram hashtag.
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