SCID: Gene therapy restored immune system in children with rare disorder

Ten children with the rare condition Artemis-deficient severe combined immunodeficiency had their immune systems either partially or fully restored with gene-replacement therapy

By Grace Wade

Children born without a working immune system due to a rare genetic disorder called Artemis-deficient severe combined immunodeficiency (Artemis-deficient SCID) may be able to lead normal lives thanks to a new gene-replacement therapy. A trial found that the therapy either partially or fully restored the immune systems of 10 infants with the condition.

Each year, between 40 and 100 babies in the US are diagnosed with SCID. It is also known as bubble boy disease, after a 1970s documentary about a child with the condition who had to live inside a sterile, plastic bubble due to the lack of a functioning immune system. Most children with SCID will die before the age of 2 unless treated with a bone marrow transplant. However, infants with Artemis-deficient SCID – a rare subtype of the condition – are less likely to have a successful transplant due to unique genetic defects.

Because gene-replacement therapy has shown promise in treating other types of SCID, Morton Cowan at the University of California, San Francisco, and his colleagues wanted to see if it could also treat Artemis-deficient SCID.

This subtype of SCID is caused by a defect in the gene that codes for the protein Artemis. Without Artemis, the body cannot produce important immune cells called T cells and B cells. The researchers extracted stem cells from the bone marrow of 10 infants with the condition and inserted corrected genetic information into the cells. The children then underwent a low dose of chemotherapy to kill cells in their bone marrow. This made space for the corrected stem cells, which were infused back into them using an IV.

Follow-up blood tests found that all the children produced T cells and B cells between six and 16 weeks after treatment. Of the six infants who received the therapy two or more years ago, five now have fully functioning immune systems. With time, the other participants should also develop fully functional immune systems, says Jennifer Puck, also at the University of California, San Francisco. The next stage of the research is to conduct trials with more children.

There were no serious side effects from the treatment itself, but researchers plan to follow the children for longer to be certain, says Cowan. The study may have also missed other potential side effects because of its small sample size, says Vincent Bonagura at the Feinstein Institutes for Medical Research in New York. But ultimately the treatment is a significant advancement in treating Artemis-deficient SCID, he says.

Journal reference: New England Journal of Medicine, DOI: 10.1056/NEJMoa2206575