• Sickle Cell Disease Gene Therapy Clinical Trial

    Gene Therapy

    Phone: 617-632-5064  

    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 pain and organ dysfunction.

    The sickle cell gene therapy clinical trial will involve a single infusion of autologous bone marrow-derived CD34+ hematopoietic stem cells (HSC) cells transduced with a lentiviral vector containing a short-hairpin RNA targeting BCL11a. This gene therapy technology turns off the gene expression responsible for the BCH11A protein that normally shuts off production of fetal hemoglobin at birth and represses the expression into childhood and adulthood.

    This approach has the distinct advantage of simultaneously "turning off" the sickle hemoglobin expression and "turning on" fetal hemoglobin. As a result, healthy fetal hemoglobin can still be produced, compensating and replacing "adult" hemoglobin that stiffen and take on the hallmark "sickle" shape that can trigger an acute sickle cell crisis.

    In pre-clinical studies, the therapy was able to achieve fetal hemoglobin levels of 80 percent, which was sufficient to prevent sickle cell vaso-occlusive crisis.

    The study will have three strata:

    • Stratum 1: ages 18-35
    • Stratum 2: ages 12-17
    • Stratum 3: ages 3-11

    Inclusion criteria includes:

    • Diagnosis of SCD with genotype HbSS, HbS/0 thalassemia, HbSD, or HbSO, and HbF <10% by electrophoresis.
    • Age 3 years to 35 years
    • Severe symptomatic SCD
    • Failure of hydroxyurea therapy
    • No HLA-genotypically identical related bone marrow donor available

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