Gene therapy effective in helping children with severe combined immunodeficiency (SCID)

A UK study in this week’s issue of THE LANCET provides further evidence that gene therapy can be effective in creating a functional immune system for infants with severe combined immunodeficiency (SCID).

SCID represents a group of rare, sometimes fatal, congenital disorders characterized by little or no immune response. The defining feature of SCID, commonly known as "bubble boy" disease, is a defect in the specialized white blood cells (B- and T-lymphocytes) that defend us from infection by viruses, bacteria and fungi. Without a functional immune system, SCID patients are susceptible to recurrent infections such as pneumonia, meningitis and chicken pox, and can die before the first year of life.

Though invasive, new treatments such as bone marrow and stem-cell transplantation save as many as 80% of SCID patients. This leaves individuals at high risk of infection, as documented many years ago by the patient, David Vetter, who lived in a ‘bubble’ for 12 years to prevent infection from the external environment. At the age of 12, David underwent a bone marrow transplant — the known cure for SCID — using his sister’s marrow. Although the goal of the procedure was to stimulate the growth of his immune system, David died Feb. 22, 1984, from a cancerous infection, an unfortunate consequence of the transplant.

In the latest study, 4 children with SCID had stem cells removed from their own bone marrow; the relevant ‘good’ gene was identified from bone-marrow cells and spliced into a leukaemia virus. This virus was then introduced back into the patients where the gene was replicated. Almost normal immune functioning became established in all 4 patients after the procedure.

Lead investigator Adrian Thrasher (Institute of Child Health, London) comments: “At last follow up, all patients were at home in normal family and social environments, without restrictions on activities or exposure.”

An accompanying commentary (p 2155) by Marina Cavazzana-Calvo and Alain Fischer (Hôpital Necker-Enfants Malades, Paris, France) discusses all clinical research done in this field: ‘Remarkably, 17 of these 18 patients had their immunodeficiencies corrected with clear and sustained clinical benefits. The data show that the results of this gene-therapy strategy are reproducible.’