A rare genetic disease that leaves children without a functioning immune system from birth has been cured with an experimental gene therapy.
The medical world knows about seven to eight thousand (often rare) genetic disorders and, on paper, gene therapy can cure many of them. This has also been shown in practice for some diseases, including beta-thalassemia and haemophilia B. Children with the congenital abnormality SCID could now also benefit from gene therapy. A new study, published in New England Journal of Medicinereports the first ten children who have undergone gene therapy and all are now healthy and living normal lives.
Why gene therapy?
Our body is made up of around 100,000 billion cells that together ensure that everything works properly. To do that, they need protein. If you think of a cell as a factory, proteins are the workers that keep this factory running. They know what to do because they have a manual at their disposal that can be found in the cell nucleus: our DNA.
The genes that make up our DNA tell us exactly what is expected of the proteins. And then there is also such a thing as RNA. Think of it as an intermediary: RNA is a copy of a piece of DNA that is used as a protein building blueprint. But sometimes there are errors in one or more genes. And if the manual is wrong, the implementation also goes wrong. In that case, you are talking about a genetic disorder. Gene therapy can correct these errors.
The bubble boy
SCID stands for Severe Combined Immunodeficiency and is caused by a DNA error in the blood stem cells. Patients with the condition do not produce certain types of immune cells, meaning the body cannot defend itself against pathogens. A cold virus that is fairly harmless to us can prove fatal to children with SCID.
For years, the only treatment that could keep children with SCID alive for more than a few months was to put the patients in a kind of incubator with sterile air. Hence the nickname ‘bubble babies’. The most famous example of this is David ‘the bubble boy’ Vetter, who lived to be 12 years old. He was also able to go outside, thanks to a suit developed by NASA (see the image at the top of this article).
A few years later, bone marrow transplantation resulted in a large number of cured patients, but the disadvantage of this is that a suitable donor is not always available. In addition, the transplant entails the necessary risks, including an increased risk of leukemia. The arrows therefore quickly switched to gene therapy. It can correct the DNA error in the blood stem cells and thus cure the disease.
Leiden University Medical Center (LUMC) achieved success in this area earlier this year. A team of doctors treated a baby with SCID – called RAG1-SCID – just a few months old. “The child has passed the treatment without problems and the immune system is responding well to the usual vaccinations for newborns,” Arjan Lankester, professor of pediatrics and stem cell transplantation, said at the time.
In the new study, ten children with Artemis-SCID – a rarer form of SCID – underwent gene therapy. The researchers had extracted stem cells from the patients’ bone marrow. A good version of the broken gene was then built into the DNA of these cells using a crippled virus. The repaired stem cells were returned to the patients.
More than two years after the first treatment, all ten children are healthy and lead normal lives. Doctors were able to stop all ongoing treatments and safely administer childhood vaccinations.
Frank Staal, professor of molecular stem cell biology at LUMC, is impressed by this result. “This is a real breakthrough for this very rare disease. But what makes the study particularly impressive is that the researchers used a low chemodose, a quarter of what they normally use.”
Before the new, corrected stem cells were given back to the children, they first had to undergo chemotherapy. Staal: “In this way, space is made in the bone marrow for the new cells, and the old ones (which contain the gene error, ed.) are cleared away.”
But that chemotherapy causes DNA damage, and the Artemis gene is needed to repair DNA damage. “That was the difficult part of this study: determining exactly the right dose of chemotherapy per child, while leaving enough room in the bone marrow for the corrected stem cells without causing too much collateral damage. The researchers succeeded with these ten patients. is hopeful and the results also look promising in the long term.”
Sources: The New England Journal of Medicine, LUMC, New Atlas
Image: Universal History Archive/Getty Images