Toward a Cure for Sickle Cell Disease: Exploring Gene Therapy (210)

5:00 pm – 6:00 pm Thursday, September 15
Sickle cell disease (SCD) is the most common inherited blood disorder worldwide. It is estimated that 300,000 babies are born with SCD every year and it occurs largely in descendants of Sub Saharan Africa. SCD is caused by a specific mutation in the beta globin gene that results in sickle hemoglobin production. Sickle hemoglobin polymerization leads to red blood cell sickling, chronic hemolysis and vaso - occlusion. Patients with SCD experience significant pain crisis and end organ damage that leads to a decreased lifespan with a median life expectancy in the United States of 43 years. At this time, the only known cure for SCD is hematopoietic stem cell transplantation (HSCT) most often with matched sibling donors.
The five year event free survival is high at approximately 90-95%. Unfortunately, only 20% of patients with sickle cell disease have matched sibling donors. HSCT for these patients is limited by availability of donors and the risk of developing life-threatening transplant related complications. This led to the pursuit of novel curative therapies including gene therapy. The goal of gene therapy is to increase fetal hemoglobin. Fetal hemoglobin produces normal red blood cells that don’t sickle. Shortly after birth, the body stops making fetal hemoglobin due to the expression of the BCL11 gene which blocks production of fetal hemoglobin and produces adult hemoglobin. Gene therapy is successful by blocking the expression of the BCL11 gene and essentially flips the switch back to fetal hemoglobin. These genetically modified genes are administered via lentiviral vector in autologous stem cells, eliminating the possibility of graft rejection and graft versus host disease seen in patient undergoing traditional hematopoietic stem cell transplant. In an effort to find more curative options for these patients, gene therapy clinical trials were undertaken and are proving to be promising.