Region’s first patient receives sickle cell gene therapy
Nebraska patient seeks cure for devastating disease from WashU Medicine pediatric specialists at St. Louis Children’s Hospital
Huy MachWashU Medicine and St. Louis Children’s Hospital are the first in the region — and among only a few academic centers in the U.S. — to begin offering a newly approved gene therapy to cure sickle cell disease. Martin Mwita Jr. (right) traveled with his mother from their home in Nebraska to St. Louis to receive the innovative treatment.
Martin Mwita Jr.’s symptoms started when he was just an infant, with painful swelling of his hands and feet, often one of the first manifestations of sickle cell disease. By the time he was a year old, he had been hospitalized multiple times due to the illness. At just 19 months, he suffered strokes and serious blood-vessel blockages in his lungs, resulting in severe complications that left him in a coma.
“We thought we had lost him,” recalled Mwita’s mom, Jacinta Mwita, of her then-toddler son. “But after three weeks in a coma, his eyes opened. It was a miracle!”
Martin Mwita, who just turned 21, was born with sickle cell disease, a life-threatening condition that makes his red blood cells sticky and prone to clumping, blocking blood flow and oxygen from reaching his muscles and organs. Oxygen deprivation leads to severe pain episodes known as crises, as well as strokes and organ damage. Monthly blood transfusions temporarily ease symptoms by introducing healthy red blood cells but can lead to complications including infections.
Mwita was diagnosed at just a few days old, and doctors said he likely wouldn’t live past age 35 because so few of his red blood cells were normally shaped and able to carry oxygen throughout his body. As a child, everyday activities such as running or riding a bike could trigger sudden, severe pain, resulting in frequent hospitalizations that, over the years, became too numerous to count. Being exposed to summertime heat waves or the chills of winter weather also could lead to pain crises. Mwita — born with an innate musical gift — still remembers breaking down crying when he couldn’t join the high school marching band, a physically demanding activity often performed on hot days. The risk of medical complications and pain episodes from dehydration was too great.
Now, Mwita has received a chance for a cure and the opportunity to live without the excruciating pain that has dominated his young life.
He recently became the first patient in the St. Louis region to receive a gene therapy newly approved by the Food and Drug Administration (FDA) for sickle cell disease. Washington University School of Medicine in St. Louis and St. Louis Children’s Hospital are among only a few academic medical centers in the U.S. that have begun offering the treatment. Shalini Shenoy, MD, a professor of pediatrics at WashU Medicine and a renowned pediatric hematologist and oncologist of Siteman Kids at St. Louis Children’s, led the orchestration of the intensive treatment.
“We could not have imagined curing sickle cell disease with gene therapy even 10 years ago, when we were doing stem cell transplants with cells obtained from suitable donors to cure patients,” said Shenoy, who treats patients with blood disorders. “It’s a huge step forward to be able to take a patient’s own blood-making stem cells and genetically modify them before putting them back into the body in such a way that allows healthy red blood cells to be produced. For Mwita, the treatment means a life outside of the hospital, free of worry about the next pain crisis interfering with school, hobbies and his future aspirations.”
Matt MillerTreatment offers hope and demands specialized clinical expertise
Each year, an estimated 2,000 children in the U.S. — most of them Black — are born with sickle cell disease, having inherited a genetic defect from both parents who carry the sickle cell trait but don’t have symptoms of the illness. The gene mutation affects the hemoglobin protein that carries oxygen in the blood, turning ordinarily disc-shape red blood cells into sickle-like crescents. When the sticky, rigid, misshapen cells clump together, they block blood flow to tissues and organs, triggering excruciating pain.
In 2023, the FDA approved two gene therapies for sickle cell disease. The therapy Mwita received is called Lyfgenia, made by Bluebird Bio. The complex medical procedure — reserved for patients with severe forms of sickle cell disease — requires specialized clinical expertise that isn’t available outside of an academic setting.
WashU Medicine physicians lead comprehensive sickle cell disease care from birth through adulthood at St. Louis Children’s — home to the largest pediatric sickle cell disease center in Missouri — and Barnes-Jewish Hospital. For more than three decades, Shenoy and her WashU Medicine colleagues at Siteman Kids at St. Louis Children’s, all expert hematologists and specialists, have been at the forefront of treating pediatric sickle cell patients with bone marrow transplants — using stem cells from a donor. But finding a suitable donor match and taking a patient through such a transplant has its own challenges, including immune complications and infections. Gene therapy relies on using a patient’s own stem cells to avoid such complications. However, patients must first be treated with high-dose chemotherapy so the genetically modified cells can be accepted by the body.
As the cutting-edge gene therapy has become available, the expertise of WashU Medicine physicians and the comprehensive care offered at St. Louis Children’s to patients with sickle cell disease have been essential to successfully providing the treatment and care during recovery.
Dr. Shenoy reassured me I would heal and go home. She gave me peace of mind.
— Martin Mwita
In St. Louis, 400 miles away from his home, Mwita spent months away from his friends and family to undergo the stem cell collection, then the treatment and recovery. He began the process in December 2024, when he received an infusion of a drug at St. Louis Children’s that encouraged his blood-making stem cells to travel from the bone marrow to the blood stream. Over a three-day period, hundreds of millions of Mwita’s cells were collected from his blood and then shipped to Bluebird Bio, a biotherapeutics company in New Jersey. Scientists there inserted a healthy hemoglobin gene into Mwita’s cells and returned them to St. Louis earlier this spring to be infused back into Mwita’s blood.
Sara MoserBefore receiving his new cells, Mwita underwent five days of intensive chemotherapy to eliminate the remaining stem cells in his bone marrow and make room for the genetically modified cells to take hold in his blood. The procedure is intended to wipe out his bone marrow and immune system, so any defective stem cells don’t compete with the new, genetically corrected red blood cells.
“The two weeks after the intensive chemotherapy were rough,” said Mwita, who as a child learned to use music, among other strategies, to cope with pain.
Mwita lost his hair, and his skin peeled. He experienced constant nausea and vomiting. Mouth sores made it impossible to eat or talk. Persistent nose bleeds sometimes lasted hours and were difficult on Mwita. Amid painful side effects — a normal and expected part of the gene therapy that can be challenging to manage — he focused on the future.
“Dr. Shenoy reassured me I would heal and go home,” said Mwita. “She gave me peace of mind.”
Shenoy — who has extensive experience managing chemotherapy’s side effects in pediatric cancer patients undergoing stem cell transplants — was with the family every step of the way. A straight shooter with a gentle demeanor, she prepared Mwita for the monthslong therapy, balancing honest conversations with support and compassion.
“Dr. Shenoy instilled confidence in us from our first conversation together,” said Jacinta Mwita. “She wasn’t just there to administer the treatment. Dr. Shenoy was present for every question, concern and struggle, keeping us calm with her strong knowledge of sickle cell disease.”
Research to improve gene therapy
Because of the intense demands of gene therapy, patients undergo extensive evaluation to ensure they are physically and mentally able to endure the extensive procedure and potentially severe side effects. Researchers at WashU Medicine envision a future where the treatment involves fewer side effects and risks, making it safer and potentially more accessible.
I look forward to riding roller coasters, wearing dresses without layering and climbing mountains for the first time in my life. I can travel without planning around hospitals and stop worrying about the weather. It’s freeing.
—Serenity Cole
John F. DiPersio, MD, PhD, the Virginia E. & Sam J. Golman Professor of Medicine, leads research that may help expedite the procedure and reduce the chances of severe side effects. Funded in part by WashU’s Needleman Program for Innovation and Commercialization, DiPersio’s group — in work led by Michael Rettig, PhD, a professor of medicine, and Peter Ruminski, an instructor in the Division of Oncology — has developed novel small molecules that induce more robust and rapid mobilization of stem cells from the bone marrow. Zachary Crees, MD, an assistant professor of medicine at WashU Medicine, leads a clinical trial that is testing whether a new drug combination that includes DiPersio’s novel small molecule can enable more cells to be collected from the blood, potentially lessening the burden on patients to undergo multiple rounds of stem cell collection.
DiPersio’s lab also is developing a non-toxic, targeted approach to the intensive chemotherapy necessary to clear stem cells from the bone marrow. The studies, in mice, led by Steve Persaud, MD, PhD, an assistant professor in the Department of Pathology & Immunology, have shown that antibodies can successfully deplete blood-forming stem cells without the severe side effects.
“High-dose chemotherapy is an effective step in the gene therapy process,” said DiPersio, “but for some of our sickest patients with sickle cell disease, the risks are too big and potentially deadly. Preserving healthy cells with a regime that avoids chemotherapy has the potential to improve the safety of gene therapy and eliminate the need for specialized care to support recovery.”
Future unlocked
Matt MillerRemarkably, six weeks after receiving his new cells, 85% of his red blood cells were healthy — an all-time high for Mwita and a percentage that will continue to increase. Shenoy gave Mwita the thumbs up to lead a normal life — he can now ride his bike or run long distances, even on bone-chilling cold or sweltering hot days.
Mwita and his mother credit his team of WashU Medicine doctors and St. Louis Children’s nurses and support staff, who were with him through every struggle and milestone. They cheered him on during his triumphant 6-mile walk through the hallways near his hospital room, a goal he set for himself during his recovery. They succumbed to joyful tears as he walked out of the hospital to begin a new chapter of his life.
But their work doesn’t stop there. WashU Medicine physicians actively participate in research to continue improving treatments and transplants for sickle cell disease, sometimes in conjunction with peers from across the country and national advocacy groups. And, of course, more and more patients will be able to receive gene therapy, just like Mwita.
Shenoy currently oversees the care of two other young patients with sickle cell disease who are receiving Lyfgenia, with several more patients awaiting approval. Serenity Cole, an 18-year-old from St. Louis, recently learned that after receiving the gene therapy, 94% of her red blood cells are producing healthy hemoglobin.
Matt Miller“I take comfort knowing that my own cells can heal me,” said Cole, who was recently discharged from the hospital. “I look forward to riding roller coasters, wearing dresses without layering and climbing mountains for the first time in my life. I can travel without planning around hospitals and stop worrying about the weather. It’s freeing.”
Now unburdened by the disease that interfered with his childhood, Mwita begins a life stage full of opportunities. Gene therapy has unlocked his future, allowing him to go back to school to study business, fully engage in an active social life and dream about starting a family one day.
Mwita and his mom left behind their temporary St. Louis apartment on Mother’s Day weekend, just in time to spend the holiday with his three siblings, including a younger sister with severe sickle cell disease who hopes to follow in her big brother’s footsteps in pursuit of gene therapy.
For more information about sickle cell treatment at WashU Medicine and St. Louis Children’s Hospital, including gene therapy, please call 314-454-KIDS.
