LentiGlobin™ for Sickle Cell Disease

Sickle Cell Disease and Thalassemia major 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 Sickle Cell Disease, the gene defect causes hemoglobin to polymerize and red blood cells to lose their normally rounded shape and to "sickle," allowing them to be trapped in the blood capillaries and to cause severe pain and organ damage. 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.

Allogeneic bone marrow transplantation from HLA-matched donors is the only known cure for Sickle Cell Disease.. 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.