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In an international effort, researchers from the University of California, Los Angeles (UCLA), and Great Ormond Street Hospital in London have successfully restored the immune function in 95 percent of children treated for "Bubble Baby" disease using an experimental gene therapy approach that involves a surprising helper – the AIDS virus.
The scientific name for bubble baby disease is severe combined immunodeficiency (SCID). There are two types, one that is X-linked which is the most common form of SCID, and another form that is caused by adenosine deaminase deficiency, called ADA-SCID.
ADA-SCID occurs due to mutations in the ADA gene that is responsible for making the enzyme adenosine deaminase, required for the correct formation of immune cells. Therefore, the condition in children causes the bone marrow not to develop the functioning immune cells required to fight off infections.
For these children, even simple daily activities like hugging a parent carry enormous risks because they could catch an infection, which can easily be life-threatening as they don't have the immune cells to protect them.
For example, back in the 1970s, a Texas boy that had X-linked SCID lived inside a protective bubble for most of his lifetime of 12 years to prevent him from catching germs, hence the phrase "Bubble Baby" disease. Children born with SCID normally don't survive long without intervention.
One approach to treat both X-linked and ADA-SCID is bone marrow transplants – however, the downside is that you require a genetically matched sibling for it to work, making the approach less common, as well as the fact that it comes with risks. At the moment, the best alternative treatment option for children with ADA-SCID is twice-weekly injections of the ADA enzyme until they find a bone marrow transplant match. But again, this approach only acts as a temporary solution, not a long-term cure.
Now, international researchers reporting in the New England Journal of Medicine have shown that a gene therapy approach using a disabled and modified AIDS virus (Lentivirus) to fix the faulty genetic mutation in children with ADA-SCID has successfully worked. It is too early to say whether the therapy permanently cured the ADA-SCID, however, the researchers feel that the one-time procedure might provide lifelong results in these children which could be extremely encouraging.
"Between all three clinical trials, 50 patients were treated, and the overall results were very encouraging," said Dr Donald Kohn of UCLA, a distinguished professor of microbiology, immunology and molecular genetics, in a statement. "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."
The approach works by taking blood stem cells from patients that have ADA-SCID. These stem cells have the potential to form all types of blood cells, including immune cells. The researchers then use a disabled form of the AIDS virus to deliver a correct copy of the ADA gene back to these stem cells and then injected the stem cells back into the children.
48 out of the 50 children with ADA-SCID that partook in the trials were successfully treated without adverse side effects or complications. For the two children where the therapy had not worked, they were able to return to standard therapies and treatments, and one later received and bone marrow transplant.
"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 a bone marrow transplant and the toxic side effects often associated with that treatment," Dr.Claire Booth a consultant in pediatric immunology and gene therapy at Great Ormond Street Hospital concluded.
