Sickle cell disease (SCD) refers to a group of blood disorders usually inherited from parents. The disease is characterized by pain, progressive organ damage, and hemolytic anemia. A higher concentration of erythrocyte fetal hemoglobin (HbF) consisting of α- and γ-globins may improve the condition. This study aims to evaluate the effect of the silencing of BCL11A, a repressor of γ-globin expression, for the induction of HbF.

This single-center, open-label pilot study included a total of six patients with SCD. The treatment therapy included the infusion of autologous CD34+ cells transduced with BCH-BB694 lentiviral vector, followed by encoding a short hairpin RNA embedded in microRNA. This enabled erythroid lineage-specific knockdown. The primary outcome of the study was engraftment and safety of the procedure.

At a median follow-up of 18 months, six patients included in the study were followed for at least six months after receiving BCH-BB694 gene therapy. All the patients who were followed up had engraftment, with adverse events being consistent with preparative chemotherapy effects. All the patients who were fully evaluated achieved stable HbF induction.

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The research concluded that BCL11A inhibition was an effective treatment for sickle cell disease and led to stable HbF induction in the involved patients.

Ref: https://www.nejm.org/doi/full/10.1056/NEJMoa2029392