An international team of scientists have developed an experimental gene therapy treatment for children with a severe immune disorder, and it’s showing promise.
As described in a paper published in the New England Journal of Medicine, clinical trials in the US and UK have successfully treated 48 out of 50 participants born with a rare and life-threatening disease known as severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID).
ADA-SCID is caused by mutations in a gene that produces an enzyme essential to a functioning immune system. If untreated, children can die from infections by the time they are toddlers.
The current standard treatment for ADA-SCID involves injecting patients once or twice weekly with the adenosine deaminase enzyme, until a bone marrow donor is found to transplant stem cell into the patient. But donors are typically only found for 20% of affected patients – those without need expensive, lifelong injections, plus antibiotics and other preventative medications.
This new gene therapy technique uses the patient’s own blood-forming stem cells. These are genetically modified to correct the deficiency, by using a viral vector to deliver a new copy of the ADA gene into the DNA.
Once returned to the patient’s body, the modified stem cells can then produce healthy blood cells able to tackle infection.
Three clinical trials treated 50 children with this gene therapy between 2012 and 2017, at the Great Ormond Street Hospital in the UK, and at the UCLA Mattel Children’s Hospital and the National Institutes of Health in the US. This new study reports the two- to three-year outcomes of the trials.
“The overall results were very encouraging,” says co-author Kohn from UCLA. “All the patients are alive and well, and in more than 95% of them, the therapy appears to have corrected their underlying immune system problems.
“Treatment was successful in all but two of the 50 cases, and both of those children were able to return to current standard-of care-therapies and treatments, with one eventually receiving a bone marrow transplant.”
The other 48 children were able to stop regular immune system replacement therapy, though they will continue to be monitored throughout their lives.
Co-author of the study, Claire Booth from the Great Ormond Street Hospital, says: “If approved in the future, this treatment could be standard for ADA-SCID, and potentially many other genetic conditions, removing the need to find a matched-donor for bone marrow transplant and the toxic side effects often associated with that treatment.
“We need and want guidelines to change so we can start offering this potential cure to children and provide it as a first-choice treatment – this research could set those wheels in motion.”