A case report published in the March 2 issue of the New England Journal of Medicine proves that gene replacement therapy can be a powerful curative tool for sickle cell disease (SCD) and paves the way for the design of similar strategies to treat other monogenic conditions of the haematopoietic system. Ribeil J.A. and colleagues describe the first SCD patient treated with LentiGlobin vector BB305, a lentiviral vector encoding a modified β-globin gene (β^A-T87Q) that confers anti-sickling properties. The patient is a 13-year-old boy with severe SCD, who was placed on a regular red-cell transfusion regimen after failure of hydroxyurea treatment to reduce his clinical symptoms. The boy underwent myeloablation with intravenous busulfan, followed by a single infusion of gene-corrected autologous bone marrow CD34⁺ stem cells. The engraftment of transduced stem cells was successful, red-cell transfusion requirements ceased 3 months after gene therapy, and by 15 months of follow-up the clinical phenotype and the biological hallmarks of SCD were substantially improved. By that time a stable vector copy number was achieved, and therapeutic haemoglobin (HbA-T87Q) levels had reached 5.7 g/dL (48% of the total Hb) with a corresponding drop in sickle haemoglobin levels. Vector integration site analyses showed polyclonal reconstitution without clonal dominance. The boy did not experience adverse events related to gene therapy, and more than 15 months post-treatment has had no hospitalization or acute SCD-related events. The clinical study (HGB-205) was sponsored by bluebird bio, with principal investigator Professor Marina Cavazzana, M.D., Ph.D.

More information: Original publication