Previous studies have investigated the potential for gene therapy using a retroviral vector to treat children with the fatal inherited disease, X-linked severe combined immunodeficiency (SCID-X1, or “bubble boy disease”).

The vector works by latching to the surface of the T cell and injecting genetic material that helps “train” the cells to properly produce their own immune cells.

While successful in earlier studies, in some cases the children developed leukaemia when new corrective genetic material was inserted near a trigger in the children’s DNA, predisposing T cells to turn into cancer cells.

Aiming to overcome this challenge and achieve immune recovery in these patients without provoking the development of leukaemia, investigators considered an approach with a modified version of the vector that was designed to insert the genetic material but not encourage overgrowth of the cells.

Enrolling nine boys with SCID-X1, investigators removed some of the boys’ bone marrow stem cells and engineered them with this new version of the vector and infused the engineered cells back into the bloodstream. After the cell infusion and adequate observation, eight of the nine boys remained alive and healthy; one patient died of advanced viral infection that was present when he entered the study.

Seven are showing signs that their bodies are properly producing healthy T cells. Analysis of insertion pattern in the blood of these children shows much less insertion of the corrective gene near trigger points for cancer compared to children enrolled on the previous trial.

“We have preliminary evidence that using this new vector approach is just as effective but may eliminate the long-term risk of leukaemia in these children,” said study author Sung-Yun Pai, MD, of Dana-Farber/Boston Children’s Cancer and Blood Disorders Center in Boston, Mass. “We will need to closely monitor these patients to evaluate their long-term risks, but at this point we are hopeful given the excellent response so far.”

Source: ASH