An experimental form of gene therapy developed by a team of researchers from UCLA and Great Ormond Street Hospital in London has successfully treated 48 of 50 children born with a rare and deadly inherited disorder that leaves them without an immune system, according to a study published Tuesday.
Severe combined immunodeficiency due to adenosine deaminase deficiency, or ADA-SCID, is caused by mutations in the ADA gene that creates the enzyme adenosine deaminase, which is essential to a functioning immune system. For children with the condition, even day-to-day activities like going to school or playing with friends can lead to dangerous, life-threatening infections. If untreated, ADA-SCID can be fatal within the first two years of life.
The new gene therapy method involves first collecting some of the child’s blood-forming stem cells, which have the potential to create all types of blood and immune cells. Next, using an approach developed by the research team, a new copy of the ADA gene is delivered into the stem cells by a modified lentivirus, or “viral vector.”
The corrected cells are then returned to the child’s body, where they are intended to produce a continual supply of healthy immune cells capable of fighting infection, according to researchers.
In the study published in the New England Journal of Medicine, co-lead authors Dr. Donald Kohn of UCLA and Dr. Claire Booth of Great Ormond Street Hospital report two- and three-year outcomes for children treated with the lentiviral gene therapy in clinical trials at the London hospital, UCLA Mattel Children’s Hospital and the National Institutes of Health between 2012 and 2017.
“Between all three clinical trials, 50 patients were treated, and the overall results were very encouraging,” said Kohn, a professor of microbiology, immunology and molecular genetics and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at 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.”
No complications or treatment-limiting events were reported among the patients. Most adverse events were mild or moderate, and were considered to be related to routine procedures performed in preparation for the experimental gene therapy treatment or effects of the immune system rebuilding, researchers said.
“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,” said Kohn, who has been working to develop gene therapies for ADA-SCID and other blood diseases for 35 years.