Gene therapy appears to have cured “baby-in-bubble” infants with a rare disorder that robs them of any immune protection.
Eight infants in the US with the condition, X-linked severe combined immunodeficiency (X-SCID), have grown into healthy two-year-old toddlers living normal lives.
Without the experimental treatment, they would have been at risk of an early death from the slightest infection.
Children with X-SCID have to live their lives in completely sterile conditions.
The disorder first hit the headlines because of the tragic case of “bubble boy” David Vetter, from Texas.
Born in 1971, David lived his whole life from birth in a plastic bubble until his death at the age of 12.
X-SCID is caused by a mutation in a gene, IL2RG, which produces a protein essential for normal immune function.
Current treatment involves a bone marrow transplant from a tissue-matched sibling donor. However, 80% of patients lack suitable donors.
The new therapy used a harmless virus to “ferry” a correct version of the IL2RG gene into the DNA of blood stem cells taken from bone marrow.
The cells were then frozen, tested, and infused back into the patients. In addition, the children were given carefully adjusted doses of a blood cancer drug, busulfan.
Within three months of the treatment, gene-corrected immune cells were found in the blood of all but one child, who needed a second course of therapy.
The immune cells included T-cells and NK (natural killer) cells, which fight infections.
Antibody-producing B cells were also present, the first time this has occurred after experimental gene therapy for X-SCID.
Dr Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases (NIAID), said: “These exciting new results suggest that gene therapy may be an effective treatment option for infants with this extremely serious condition, particularly those who lack an optimal donor for stem cell transplant.
“This advance offers them the hope of developing a wholly functional immune system and the chance to live a full, healthy life.”
The findings are published in the New England Journal of Medicine.
A number of previous attempts to treat X-SCID with gene therapy have failed.
The new treatment, developed at St Jude Children’s Research Hospital in Memphis, US, was designed to prevent the therapy accidentally causing leukaemia.
A major factor was the introduction of busulfan, which makes space in bone marrow for donor stem cells to grow.
Co-author Professor Mort Cowan, from the University of California at San Francisco, said: “We found that the addition of very low doses of busulfan .. increased the engraftment of gene-corrected stem cells in the bone marrow without causing the side effects associated with standard doses.”
Dr Ewelina Mamcarz, from the St June Department of Bone Marrow Transplantation and Cellular Therapy, said: “These patients are toddlers now, who are responding to vaccinations and have immune systems to make all immune cells they need for protection from infections as they explore the world and lead normal lives.”