In the United States, for the first time, eight children born without immune defense were saved thanks to combined chemotherapy and gene therapy with the AIDS virus (HIV).
A world first. In the US, eight newborns with "baby bubble syndrome", a rare genetic disease affecting just one in 200,000 births, have been saved thanks to a new treatment. The latter, which combines chemotherapy and gene therapy with the AIDS virus (HIV), has been described in detail in an article published on April 18 in The New England Journal of Medicine.
To treat children born without immune defense and condemned to spend their lives in a cut bubble of the world and its microbes, the doctors of the St. Jude hospitals of Memphis and the Benioff Children of the University of California had the idea of add chemotherapy to the traditional gene therapy that involves taking stem cells from the patient to inject the missing gene into the laboratory.
Usually used against cancer, chemotherapy was here to remove all the cells in the patient's bone marrow. "Until now, we did not do it because it was thought that it was to make him take an additional risk," says Anne Galy director of research at Inserm / Genethon at Figaro. "If you remove your bone marrow and then the graft does not take, it permanently loses its immune system." Realizing that chemotherapy was the only way to transplant the entire immune system sustainably, the researchers took the risk.
HIV synthesized in the laboratory
In addition, they used the human immunodeficiency virus, better known as HIV, to transport the gene to the heart of the cells. "The advantage of HIV is that it makes it very easy to insert a copy of the normal gene into the cells' DNA," explains Anne Galy. This kind of virus "is synthesized in the laboratory, as drugs are, but not infectious.We only keep the properties we are interested in. It's a bit like a shell," says the researcher. This technique has been used for a long time in gene therapies.
And it worked perfectly. One month after receiving the treatment, only one baby had to receive a second dose. A year later, the eight children are out of the woods. "These patients (...) respond to the vaccines and have an immune system that allows them to make all the immune cells they need to protect themselves from infections," says Dr. Ewelina Mamcarz, co-author of the study and a physician in the service of bone marrow transplant and cell therapy at St. Jude Children's Hospital Memphis.
"Although longer follow-up is needed to evaluate the late effects of treatment, these results suggest that most patients treated with this gene therapy will develop a lasting and complete immune response with no side effects," added Dr. Mort Cowan, pediatrician at Benioff Children's Hospital, University of California, San Francisco.
Thus, the researchers "hope that this therapy, which includes several novelties, will serve as a basis for the development of gene therapies to treat other devastating blood diseases". At present, these therapies only occur in clinical trials and several patients treated in this way have subsequently developed leukemia or seen the effects of treatment being exhausted after 15 to 20 years. A few years ago, however, a Franco-American trial had already been successful, healing seven baby bubbles.
A very limited life expectancy
Severe combined immunodeficiency is best known as "Bubble Boy Syndrome", referring to the first patient with the disease in 1971, David Vetter, who had to spend his short life in a bubble to protect himself from potential infections. . This disease is due to the absence of a structure on the surface of the cells of the immune system, otherwise the cells are like blind: they can not move, do not proliferate, they do not activate, explains Anne Galy.
A deficit caused by an error in the genetic code. Babies born with this syndrome therefore have an immune system but it is as if it were extinguished. And if, at delivery, the baby seems healthy, very quickly, he begins to catch all kinds of infections (pneumonia, meningitis, septicemia ...) that put his life in danger. If no action is taken, its life expectancy is very limited. Thus, David Vetter died at the age of twelve despite a bone marrow transplant, the treatment most used to treat baby bubbles.
Unfortunately, in addition to being extremely restrictive (taking immunosuppressive drugs for life, developing cancers), this solution is not universal. In fact, children who do not have compatible donors around them have all the risks of rejecting the transplant. That is why today's prowess paves the way for exciting new prospects.