Three-year-old Bryce Gross meets with Mitch Weiss, MD, PhD, Hematology chair, and nurse practitioner Nicole Dockery.
Adrienne Gross knows firsthand the sound a mother’s heart makes when it shatters into a million glittering pieces. Hers did just that in September of 2013 when she learned that Bryce, her adorable newborn son, had a life-threatening disease.
Time began to move slowly. “This is not my life,” she thought. “This is not my son. This is not my situation.”
Although Adrienne knew she carried the trait for sickle cell disease, neither she nor her husband, Bruce, knew that he was also a carrier. That meant they had a 1-in-4 chance of having a child with the disorder. Bryce’s older sister, Chloe, had been born without the disease.
“Everyone I knew who had sickle cell had died,” Adrienne says. “I didn’t know anyone who had the disease and was living a normal life. I didn’t even know how to process that information.”
Night and Day
Soon afterward, Bruce and Adrienne learned that St. Jude Children’s Research Hospital was poised to help.
“Everything changed when we met with a staff member from St. Jude,” Adrienne recalls. “A feeling of hope came over us. It was like, ‘This is not the end of the world. We are going to walk through this journey with you, with Bryce. This is something that’s going to be a part of your life, but it’s not the end for your family or your son.’”
About 100,000 people in the U.S. have sickle cell disease, an inherited disorder that causes red blood cells to become hard and crescent-shaped, instead of soft and round. The misshapen cells block blood flow, causing intense pain, stroke, the need for blood transfusions and a shortened life expectancy. The disease can ravage the lungs, brain, heart, spleen, kidneys, eyes, joints, skin and liver.
During Bryce’s first year of life, his family visited the hospital regularly. At those visits, St. Jude staff educated them about the disease and introduced them to a family support group. Bryce experienced his first pain crisis at age 1. Soon afterward, he began taking a medication called hydroxyurea.
“Before he began taking hydroxyurea, his hands and feet would swell. He didn’t want to be touched because he was in so much pain. Any change in his environment would make him sick,” Adrienne recalls. “After he started taking the medication—it was like night and day.
“I know what it feels like to be low and scared and sad,” she continues, “but now we have a normal life. Every now and then we go to the doctor or the hospital, but that happens in people’s lives who don’t have to deal with sickle cell. We have learned how to be thankful. We celebrate the good days, and we count our blessings.”
Building on a Legacy
St. Jude scientists have been researching sickle cell disease for more than half a century:
- Before the hospital opened in 1962, its first research grant was awarded to Lemuel Diggs, MD, for the study of sickle cell disease.
- A St. Jude patient was the first person in the world to be cured of the disorder through a stem cell or bone marrow transplant.
- Sickle cell pioneer Winfred Wang, MD, of St. Jude Hematology, led nationwide research to advance the use of hydroxyurea in children.
- St. Jude scientists discovered ways to detect and prevent stroke risk in children with sickle cell disease.
St. Jude President and Chief Executive Officer James R. Downing, MD, is building on that legacy. He recently unveiled a plan to enhance the hospital’s sickle cell program. It’s great news for Bryce and for the 2,000 other children born with the disease in the U.S. each year.
Sweet Relief
Scientists and clinicians throughout St. Jude are seeking ways to provide the best possible care for children with the disease.
Hydroxyurea treatment
Twenty years ago, St. Jude clinicians pioneered the use of hydroxyurea to relieve the symptoms of sickle cell disease.
“It’s been a long saga,” recalls Wang, who has been at St. Jude since 1979. Wang headed the first national studies to use the drug in children. “We found that it’s effective for symptoms and blood counts, and that it’s reasonably safe to give hydroxyurea to very young children with sickle cell anemia.”
Today, St. Jude researchers continue to refine the use of this drug. Jeremie Estepp, MD, of St. Jude Hematology, is currently leading a study to learn how to optimize the use of hydroxyurea and to maximize its short- and long-term benefits.
Precision medicine and pain relief
Another faculty member, Mary Relling, PharmD, St. Jude Pharmaceutical Sciences chair, discovered a way to use genetic testing to determine which children should and should not receive codeine, a drug often prescribed to relieve the severe pain of sickle cell crises.
For most people, codeine works as intended. But the drug is dangerous for individuals who have an active gene that makes them metabolize codeine too quickly. And for about 10 percent of patients, the drug will not work at all.
“Now we know who benefits the most from codeine,” says Mitch Weiss, MD, PhD, Hematology chair. “This is precision medicine, because by knowing a child’s genetic status, we can decide which pain reliever is most likely to be safe and effective in that patient.”
Sickle cell on trial
St. Jude research is ongoing to solve the problems of iron overload, stroke and learning disabilities that may accompany sickle cell disease. During the next few years, researchers will focus on further reducing complications, expanding the number of clinical trials available.
As part of one new study, St. Jude will sequence the genome of 1,000 patients with sickle cell disease. Scientists will use data from that study to determine how genes affect sickle cell patients through their lifetime.
“Why are some patients sicker than others?” Weiss muses. “There’s a strong genetic component to that. Through this study, we believe we can better understand the genetics.”
Sickle cell pioneer Winfred Wang, MD, (pictured with Lundan Brown) led nationwide research to advance the use of hydroxyurea, which is currently the only approved drug for the disease.
Destination: Cure
But the ultimate dream of St. Jude clinicians and researchers is to find a cure.
“Most programs in sickle cell disease have focused on decreasing symptoms,” Downing explains. “Well, why not try to cure it? Can we use gene therapy to do that? Can we use gene editing to cure it? Can we find better drugs that would essentially reverse the disease? We’re expanding our research efforts in those areas.”
Stem cell or bone marrow transplant is the only known cure for sickle cell disease. But this procedure requires a matched donor and poses dangers from infection and other side effects.
“We have much to learn about transplants and how to do them better for this population,” Weiss says. That’s why the hospital is working to develop a leading bone marrow transplantation program for children with sickle cell disease. This program will identify children who will benefit the most from transplants, develop new clinical trials to improve engraftment rates and devise ways to decrease transplant-related side effects.
Gene therapy replaces the mutated sickle cell gene with a normal gene. Sickle cell disease is caused by a change in the beta-globin gene. The resulting abnormal proteins cause red blood cells to adopt their sickled shape. Through gene therapy, scientists will insert a normal gene into a harmless virus that would transport that healthy gene into the cells’ DNA.
Gene editing involves clipping out the mutant part of the faulty DNA and replacing it with a piece of normal DNA. St. Jude researchers are exploring this technique to edit the genome.
“There have been two revolutions in biology in the past 10 years,” Weiss observes. “One is the ability to sequence the genome so easily, and we have taken advantage of that at St. Jude through our Pediatric Cancer Genome Project. The second revolution is the technique called gene editing. It holds great promise for changing a sickle cell mutation back to normal.”
A Mother's Dream
Bryce’s mom has often wondered whether she will see a cure for sickle cell disease in her lifetime.
“We know we are in the right place and at the right facility and with the right researchers, who believe there is a cure out there for these kids,” Adrienne says. “Just to know that they are focusing on cures and having these conversations gives us hope.”
More articles from this issue
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Patient to Pioneer
Read about how St. Jude prepares to move whole-genome sequencing into the clinic.
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Solving Mysteries of the Microbiota
St. Jude scientists learn more about how bacteria affect colon cancer and the body’s immune system.
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The Future Starts Now
When it comes to sickle cell disease, St. Jude researchers have their sights set on the future.
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Flexing Mental Muscles
Computerized cognitive training improves attention and memory in childhood cancer survivors.
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From Old Drugs, New Hope
Scientist redesigns an existing antibiotic to combat drug-resistant infections.
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Family First
One couple’s generosity nurtures their St. Jude “family.”
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Up Your Game
Video gamers unite to raise funds for the hospital.
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St. Jude Heroes
A St. Jude patient joined more than 21,00 others to participate in the St. Jude Memphis Marathon.
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Research Highlights
Read recent highlights from St. Jude, including a discovery that could help newborns and preventing blockages before they develop.