An experimental form of gene therapy developed by a team of researchers at UCLA and Great Ormond Street Hospital in London has successfully treated 48 out of 50 children born with a rare and deadly inherited disorder that leaves them without an immune system.
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 for the functioning of the immune system.
For children with the condition, even everyday activities, such as going to school or playing with friends, can lead to dangerous, life-threatening infections. If left untreated, ADA-SCID can be fatal within the first two years of life.
The investigational gene therapy method involves first collecting some of the child’s blood-forming stem cells, which have the potential to create all kinds of blood and immune cells.
Then, using an approach developed by the research team, a modified lentivirus or “viral vector” delivers a new copy of the ADA gene to stem cells. The corrected cells are then returned to the child’s body, where they are destined to produce a continuous supply of healthy immune cells capable of fighting infection.
In a study published in the New England Journal of Medicine, co-lead authors, UCLA Dr. Donald Kohn and Great Ormond Street Hospital Dr. Claire Booth, or GOSH, report two- and three-year outcomes for children treated with investigational lentiviral gene therapy in clinical trials between 2012 and 2017.
“Across the three clinical trials, 50 patients were treated and the overall results were very encouraging,” said Kohn, distinguished professor of microbiology, immunology and molecular genetics at UCLA. “All the patients are alive and well, and in more than 95% of them, the therapy appears to have corrected the underlying immune system problems.”
No complications or events limiting treatment were reported among patients. Most adverse events were mild or moderate and were considered to be related to routine procedures performed in preparation for experimental gene therapy treatment or the effects of rebuilding the immune system.
“The treatment was successful in all but two of the 50 cases, and both children were able to return to current standard therapies and treatments, with one of them eventually receiving a bone marrow transplant,” said Kohn, who has been working to develop therapies. genetics for ADA-SCID and other blood diseases for 35 years.
Investigational gene therapy, a one-time procedure that researchers say can provide lifelong results, is a welcome new potential treatment option for children with ADA-SCID, who otherwise must undergo one or more injections. twice a week of the ADA enzyme until a compatible bone marrow donor can be found, usually a close relative.
If a donor is not available, patients require lifelong injections, along with antibiotics, antifungal medications, and monthly infusions of immunoglobulin, which contains antibodies that fight infection. These treatments are expensive and therefore out of reach for patients in many countries.
“If approved in the future, this treatment could be standard for ADA-SCID and potentially many other genetic conditions, eliminating the need to find a compatible donor for a bone marrow transplant and the toxic side effects that are often associated with that treatment, “said Booth, a GOSH consultant in pediatric immunology and gene therapy.
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