Columbia University Medical Center

Gene Therapy Holds Promise For Sickle Cell Disease

Researchers from Columbia University College of Physicians & Surgeons have demonstrated the long-term transfer and high level long-term expression of the normal human beta globin gene in an animal model for the first time. The study, published in the Nov. 1 issue of Blood, may lead to gene therapy for the treatment of sickle cell disease and beta thalassemia, a related disorder. Senior author Arthur Bank, M.D., FACP, professor of medicine and genetics & development and director of the division of hematology at Columbia University, and colleagues put a human beta globin gene into a safe retrovirus and added the virus to mice bone marrow cells in vivo. The modified cells were then transplanted into mice. The researchers were able to detect the presence of the human beta globin gene up to eight months later. In addition, the researchers documented high levels of expression of the gene. In one mouse, 20 percent of the total beta globin it produced was from the human beta globin gene.
“If we could attain that level of normal human beta globin gene expression in a patient with sickle cell disease or beta thalassemia marrow cells, it would be enough to expect to ameliorate, if not cure, the anemia of patients with sickle cell disease and beta thalassemia,” says Bank”

In sickle cell disease, the beta globin gene produces an abnormal form of hemoglobin, the oxygen-carrying molecule in the blood. The damage causes red blood cells to distort and alter their shape. In beta thalassemia, the gene produces inadequate levels of hemoglobin. Theoretically, gene therapy that inserts a normal form of the beta globin gene into the bone marrow cells of patients could cure these diseases.

“For more than 10 years researchers have been looking for a stable delivery system to transfer and express the human beta globin gene for extended periods of time. This is the first time researchers safely and efficiently transferred the normal globin and ensured that the gene produced normal levels of its protein over long periods of time,” says Dr. Bank.

Researchers are investigating improved gene transfer systems in mouse models of sickle cell disease and beta thalassemia and developing better ways to transfer retroviruses into human hematopoietic stem cells. In addition to Dr. Bank, the authors of the paper were Dr. Harry Raftopoulos and Maureen Ward of Columbia University, and Dr. Philippe Leboulch of Harvard Medical School and the Massachusetts Institute of Technology.

The study was funded by the National Institutes of Health; the Cooley’s Anemia Foundation; and the Ahepa Anemia Foundation.

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