LentiGlobin™ for Thalassemia

Thalassemia major and sickle cell disease are caused by inheritance of defects involving the molecular structure or the production of hemoglobin, the protein in red blood cells that carries oxygen from the lungs to the tissues of the body. In Thalassemia major, the genetic defect causes reduced production of normal hemoglobin and insufficient red blood cells to sustain normal metabolism. Disease symptoms usually begin in early childhood and tend to worsen with increasing age, often resulting in organ failure and premature death. Patients typically require repeated red blood cell transfusions to lessen effects of their disease, which over time contribute to further adverse side effects. Lack of beta-globin causes fatal anemia. Patients must wear an uncomfortable pump for iron removal for 12 hours per day.

Allogeneic bone marrow transplantation from HLA-matched donors is the only known cure for Thalassemia. However, only 20% of patients have such matched donors, and those that do must be on life-long immunosuppression and risk graft vs. host disease. In current Phase I/II clinical trials, LentiGlobin™ introduces a fully-functional human hemoglobin gene under the control of the hemoglobin-promoter into the patient's own hematopoietic stem cells in the bone marrow. By adding a single transduction step to the routine practice of bone-marrow transplantation, LentiGlobin™ thus may extend the benefit of bone-marrow transplantation to the other 80% of patients who do not have matched donors.