Gene Therapy for Transfusion-Dependent Beta Thalassemia
What is transfusion-dependent beta thalassemia?
Beta thalassemia is an inherited blood disorder that affects the production of normal hemoglobin, a protein in red blood cells that carries oxygen to tissues throughout the body. It is caused by mutations in a gene called beta-globin. The most severe form of the disease requires lifelong blood transfusions every two to five weeks (thus these patients are “transfusion-dependent”). Patients must be constantly monitored for complications caused by the disease as well as the transfusions, which cause iron to accumulate in the liver, spleen, heart and other organs.
Learn more about beta thalassemia.
How is gene therapy used to treat transfusion-dependent beta thalassemia in children?
The only FDA-approved gene therapy for beta thalassemia brings back normal red blood cells. It works by putting functional copies of the abnormal gene into a patient’s own blood stem cells. The red blood cells are then able to make normal or near normal levels of hemoglobin. Other types of gene therapy for beta thalassemia that are being studied edit a different gene that restores good red cell function.
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Narrator: Our team at Children's Hospital of Philadelphia wants to help you understand ex vivo gene therapy. But before we can get into what ex vivo means, we should start by explaining, what is gene therapy? Gene therapy is a way to treat or prevent disease by using genetic material like DNA. First, the basics.
Our bodies are made up of cells, and inside each cell, is its DNA. DNA is divided into short sections called genes. Genes act as instruction manuals, telling ourselves how to make proteins. Proteins are necessary for our bodies to function. Proteins do important work, like helping us digest food and helping our blood clot when we get a cut.
But sometimes, a gene's instructions for making a protein are not correct. This can cause changes in how a protein works. These incorrect instructions can result in a genetic disease. Gene therapy can deliver new instructions to the body to make proteins that function correctly.
Paulina: My leukemia kept coming back. After receiving ex vivo gene therapy, my body was able to conquer the cancer cells.
Narrator: How does gene therapy work? There are two types of gene therapy, ex vivo and in vivo. In vivo means inside the body. When a child receives in vivo gene therapy, that means they'll get an injection or an infusion to fix defective genes.
Ex vivo means, outside the body. Let's talk more about how ex vivo gene therapy works. For ex vivo gene therapy, we remove a child's cells and modify them in a lab. We can either add a new gene or fix the gene that is causing the disease. The modified cells are then returned to the patient. This can require pre-treatment and an infusion during a hospital stay, or in other cases, it can require a stem cell transplant procedure.
One condition that can be treated with an ex vivo gene therapy is sickle cell disease, which is a blood disease that causes episodes of terrible pain. People with this disease now can receive ex vivo gene therapy that fixes the problem.
Temi: Because I received gene therapy for sickle cell disease, I am living a pain-free life.
Narrator: Gene therapy is changing and saving children's lives, and CHOP has been at the forefront of gene therapy breakthroughs from the start. CHOP was the first in the world to use an ex vivo gene therapy to treat a child with leukemia, and we've pioneered many other groundbreaking discoveries. Our determined researchers are exploring the use of ex vivo gene therapy for all kinds of diseases, so that more children worldwide will have bright futures.
Transfusion-dependent beta thalassemia treatment options at CHOP
CHOP is the first Qualified Treatment Center offering the only FDA-approved treatment, called Zynteglo. More of these FDA-approved treatments could become available in 2023. At CHOP, the gene therapy is provided through a partnership between the Thalassemia Center, the Sickle Cell and Red Cell Disorders Curative Therapy Center (CuRED), and the Cellular Therapy and Transplant Section (CTTS). A key part of CuRED’s role involves counseling patients with beta thalassemia on whether gene therapy is an appropriate treatment option. CTTS and CuRED work to prepare the patient for gene therapy, which is then administered by CTTS.
FDA-approved gene therapy
In August 2022, the FDA approved beti-cel (brand name Zynteglo®), the first potentially curative gene therapy for people with transfusion-dependent beta thalassemia. The treatment is manufactured by bluebird bio. The FDA approval was based on clinical trial data from multiple study sites, including CHOP. Janet Kwiatkowski, MD, MSCE, Director of the Thalassemia Center, served as CHOP lead investigator for the three clinical trials that led to the FDA approval, and as overall coordinating investigator for one of the studies. Alexis Thompson, MD, MPH, Chief of the Division of Hematology, was a lead investigator of the phase 3 clinical trials and presented before the FDA Advisory Committee ahead of approval. Stephan Grupp, MD, PhD, Section Chief of the Cellular Therapy and Transplant Section, leads the team that administered the therapy in the trials.
In January 2024, the FDA approved exagamglogene autotemcel (exa-cell, brand name Casgevy™) for the treatment of transfusion-dependent beta thalassemia in patients 12 years and older. In July 2026, the FDA expanded the use to patients 2 years and older.
Clinical trials for transfusion-dependent beta thalassemia
There are currently active gene therapy clinical trials for transfusion dependent beta thalassemia:
- Check back for an up-to-date list of trials
Rahemeen no longer needs regular blood transfusions, and her future has been transformed, ever since she received a curative gene therapy for her inherited blood disorder.
