The St. Jude team overcame the obstacle posed by the large number of defective hematopoietic stems cells (HSCs) producing faulty red blood cells in beta-thalassemia or sickle cell disease. The large numbers of defective HSCs thwart attempts by gene therapy to reverse the disease. HSCs are parent cells in the bone marrow that give rise to blood cells.

The researchers also performed the difficult task of integrating genes into an HSC's own DNA so the HSCs function normally.

St. Jude investigators said their results offer promise for developing gene therapy to treat blood diseases in humans caused by defective hemoglobin, i.e., hemoglobin that either lacks a critical protein called beta-globin or that contains a mutated form of the protein. Hemoglobin is the oxygen-carrying protein in red blood cells. Replacing red blood cells that carry defective hemoglobin with red cells that have normal hemoglobin is a potential strategy for curing these disorders.

Beta thalassemia (Cooley's anemia) occurs when the hemoglobin molecule lacks the beta-globin molecule that is part of the hemoglobin molecule. Children with untreated thalassemia have reduced production and survival of their faulty red blood cells. Left untreated, children with this disease die in the first decade of life. When treated by transfusions that supply normal blood cells, these children can survive into their late teens. But unless they are also treated for iron overload from blood transfusions they will eventually succumb to heart failure.

In sickle cell disease, an abnormal gene for beta-globin causes hemoglobin molecules in the red blood cell to clump together and distort the cell into the shape of a sickle. Instead of flow
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Contact: Bonnie Cameron
bonnie.cameron@stjude.org
901-495-4815
St. Jude Children's Research Hospital
1-May-2003