EMamcarz et al could successfully restore immunity in infants born with X-linked severe combined immunodeficiency (SCID-X1) through experimental gene therapy. X-SCID is caused by mutations in the IL2RG gene that makes individuals highly susceptible to severe infections. Scientists carried out the gene therapy approach in 8 infants diagnosed with X-SCID. Hematopoietic stem-cells were derived from a patient’s bone marrow. Then, an engineered lentivirus that cannot cause illness was used as a vector to deliver the normal IL2RGgene to the cells. Finally, the stem cells were infused back into the patient, after having received a low dose of the chemotherapy medication busulfan to help the genetically corrected stem cells establish themselves in the bone marrow and start producing new blood cells. Seven of the eight infants developed normal numbers of multiple types of immune cells, including T cells, B cells and natural killer (NK) cells, within three to four months after gene therapy. A second infusion of the genetically modified stem cells could greatly increase T cells in the eighth infant. IgM levels were normalized in seven of the eight infants, of whom four discontinued intravenous immune globulin supplementations. Researchers revealed that the new approach utilising lentivirus appears safer and more effective than previously tested gene-therapy strategies for X-SCID and could be performed in cases where matching sibling donors are unavailable.
Source: The New England Journal of Medicine 18 April 2019 DOI: 10.1056/NEJMoa1815408 https://www.nejm.org/doi/full/10.1056/NEJMoa1815408