A Phase I Open Label Study of Hematopoietic Stem Cell Gene Transfer for Sickle Cell Disease
Sickle cell disease is an inherited blood disorder that primarily affects children of African descent and Hispanics of Caribbean ancestry. Sickle cells tend to cluster together and stick to the lining of blood vessels, creating blockages and stopping the movement of healthy, oxygen-carrying blood, which can cause severe pain and dangerous organ dysfunction.
The sickle cell gene therapy clinical trial will involve a single infusion of autologous bone marrow-derived CD34+ hematopoietic stem cells (HSC) transduced with a lentiviral vector containing a short-hairpin RNA targeting BCL11A. This gene therapy technology turns down the expression of the BCL11A protein that normally shuts off production of fetal hemoglobin shortly after birth and represses the expression into childhood and adulthood. Fetal hemoglobin functions perfectly well to carry oxygen in red blood cells in children and adults and protects cells from sickling.
This approach has the distinct advantage of simultaneously "turning off" the sickle hemoglobin expression and "turning on" the protective fetal hemoglobin. As a result, healthy fetal hemoglobin can be produced, replacing sickle hemoglobin that can trigger an acute sickle cell crisis and other complications of sickle cell disease.
In pre-clinical studies, the therapy was able to achieve fetal hemoglobin levels of up to 80 percent, which was sufficient to reduce sickle hemoglobin to less than 20%, a level predicted to prevent sickle cell vaso-occlusive crisis.
The study will have three strata:
A patient with a severe form of sickle cell disease is symptom-free after gene therapy knocked down BCL11A and restored fetal hemoglobin production.
Sung-Yun Pai, MD, explains gene therapy.
Manny shares many loves with his little brother but one thing he wishes they didn't share is sickle cell disease (SCD). By becoming the first patient to participate in a new clinical trial, he's hoping to change that.