According to a recent article, a new stem-cell-based gene therapy is showing promising results for treating beta (β)-thalassemia in a phase 1 clinical trial.

Beta Thalassemia

Beta thalassemia is a blood disorder characterized by reduced levels of hemoglobin. Hemoglobin is the iron-rich, oxygen-carrying protein found in red blood cells.  The main function of red blood cells is to carry oxygen all throughout the body. There are three types of beta thalassemia, which indicate severity:

• Minor
• Intermedia
• Major

Those with beta thalassemia minor often are asymptomatic or experience very minor symptoms while those with major often require lifelong medical care to mitigate symptoms. Those with intermediate fall in the middle. While relatively rare in the United States, beta thalassemia is one of the most common autosomal recessive disorders in the world and has a 1 in 100,000 incidence rate.

Symptoms:

The characteristic symptom of beta thalassemia is anemia. Further symptoms include:

• Fatigue
• Weakness
• Shortness of breath
• Dizziness
• Headaches
• Blood clots
• Pallor
• Splenomegaly

Those with beta thalassemia major and intermedia may develop excess levels of iron in the body (iron overload), which primarily results from repeated blood transfusions.  Iron overload can cause a variety of symptoms affecting multiple systems of the body but can be treated by specific medications.

The Gene Therapy

The Memorial Sloan Kettering Cancer Center has spent decades researching new treatment options for patients with the inherited blood disorder beta thalassemia. The usual treatment for this disease is red blood cell transfusions that take place regularly and are needed for a patient’s entire life. Therefore, the researchers wanted to find a different option for patients.

The gene therapy works by first extracting blood stem cells from a patient, then a β-globin gene that properly functions is introduced into the stem cells, and finally, the good β-globin gene is inserted with a vector. After this process, patients then receive chemotherapy as a way to stop the body from producing blood cells and they receive their own genetically engineered stem cells infused back into them. The stem cells are then able to begin making healthy blood cells with normal β-globin.

The Next Step

Michel Sadelain, MSK physician-scientist and leader of this approach, is planning to continue monitoring the patients already involved in the trial, and continue to improve the vector and its use. He is also hoping to find ways to prevent clonal expansion (white blood cell multiplication). Although there are still quite a few factors to work through, especially when it comes to safety concerns and efficiency of administering the therapy, Sadelain will continue to work with his team on this treatment.