Children born with rare immune disease still healthy ten years after gene therapy

Gene therapy given to children born with a deadly immune disease remains safe and effective ten years on, researchers report.

A study from the University of California Los Angeles followed-up on patients who received gene therapy a decade ago to treat the immune disorder known as adenosine deaminase–deficient severe combined immunodeficiency (ADA-SCID). They found that nine out of ten children remained disease free after the one-off treatment, which used a modified virus to insert a healthy copy of the dysfunctional gene into the patient's blood stem cells.

'What we saw in the first few years was that this therapy worked, and now we're able to say that it not only works, but it works for more than ten years,' said Professor Donald Kohn, senior author of the study. 'We hope someday we'll be able to say that these results last for 80 years.'

The only child who did not gain immune function was the oldest at 15 at the time of treatment, while the others were still babies when they were treated. None of the children experienced complications from the treatment. However, the study found interesting differences in the immune response among successfully treated children, with differences up to a hundred times in the number of stem cells which contained the corrected ADA gene. Those with more corrected cells had the best immune response, while some children with few cells still required regular infusions of immunoglobulins to maintain immune function.

'What these results tell us is that there's a formula for optimal success for ADA-SCID, and it involves correcting more than five to ten percent of each patient's blood-forming stem cells,' said Professor Kohn. 'The relationship between the levels of gene-corrected cells and immune system function has never been shown so clearly before.'

Typical treatment of ADA-SCID involves either twice weekly injections of the functional ADA enzyme or a bone marrow transplant. Both of which are expensive and risk being ineffective.

Although gene therapy could be lifesaving the method used in these children has not been approved by the FDA. In part, because the virus used was shown to risk cancer development by disrupting genes involved in cell growth. While cancer was not seen in any children in the study, Professor Kohn now uses different viruses which do not carry this risk.

Professor Kohn is nevertheless encouraged by the latest report: 'Knowing that a gene therapy can have this lasting effect in ADA-SCID for more than a decade is important for our path forward as we develop new gene therapies for this and other diseases'.

This research was published in the journal Blood.