MSKCC: Clinical Trial for Beta-Thalassemia Brings Important Insights for Treating Blood Disorders with Stem Cell Gene Therapy

After three decades of research, Memorial Sloan Kettering Cancer Center investigators may have found a new treatment option for patients with an inherited blood disorder called beta (β)-thalassemia. The approach, led by MSK physician-scientist Michel Sadelain, involves using a new stem-cell-based form of gene therapy. Results from a phase 1 clinical trial testing this treatment were reported in Nature Medicine on January 3, 2022.

Here, Dr. Sadelain, who leads MSK’s Center for Cell Engineering, describes the trial’s most important findings. He also explains how the potential new treatment is a culmination of more than three decades of research by MSK investigators in the Center for Cell Engineering, the Cell Therapy and Cell Engineering Facility, and the Department of Pediatrics.

What is β-thalassemia and how is it treated?

In people with β-thalassemia, the red blood cells cannot make a protein called β-globin due to an inherited genetic mutation in the β-globin gene. This reduces the production of hemoglobin, which is the part of red blood cells that carries oxygen throughout the body. In sickle cell disease, a related disorder affecting the same gene, the red blood cells make an abnormal form of β-globin.

Together, β-thalassemia and sickle cell disease are the most common severe hereditary blood disorders in the world. An estimated 15 million people are affected by β-thalassemia alone, and even more by sickle cell disease. While sickle cell disease is better known in the US, β-thalassemia is primarily found in populations of Mediterranean, Asian, and African descent.

The current treatment for β-thalassemia is a lifetime of regular red blood cell transfusions — sometimes as often as every few weeks — which are lifesaving but can have serious secondary complications. Bone marrow or stem cell transplants can offer a cure, but most patients are unable to find a matched donor.

With this research, we want to train the body to produce normal red blood cells. We are looking to do this by genetically modifying stem cells in the bone marrow. These stem cells give rise to all the different types of blood cells.

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