Researchers from Leiden University Medical Center successfully treated a baby with the serious immune disease SCID with its own genetically modified stem cells. They fixed an error in the DNA of his blood stem cells. It is the first baby worldwide to be treated with the gene therapy developed in the Netherlands. The boy is now thirteen months old and doing well.
“A milestone,” says his pediatrician Arjan Lankester, professor of pediatrics and stem cell transplantation. “His immune system responds well to all childhood vaccinations.”
The researcher who took the first steps in the research 17 years ago was moved to tears when after two months blood tests showed that the child’s immune system had started to work. “A full month earlier than expected,” says professor of molecular stem cell biology Frank Staal. “It worked better than in the mice experiments.”
Defense against infections
The boy was born with the rare hereditary condition RAG1 SCID (Severe Combined Immunodeficiency† Children with this disease have no immune system: due to an error in the RAG1 gene, there are no B cells and T cells, white blood cells that are necessary for defense against infection. Without treatment, they often die within a year – the boy’s parents lost a child with the same condition ten years ago.
The most famous patient with the disease SCID is the American David Vetter, who is nicknamed ‘bubble boy‘ got. He lived in a sterile transparent tent from his birth in 1971. He died in 1984 of an infection after a bone marrow transplant.
SCID patients can be cured with a transplant of stem cells from the bone marrow of a healthy donor. “But a suitable donor is often difficult to find, and in 1 in 4 patients there is a rejection reaction,” says Lankester. “By repairing the child’s own stem cells, you circumvent these problems and there is a much better chance of recovery.”
Three months after the birth of the child, the researchers collected stem cells – cells that were not yet specialized from which all blood cells would later develop. They built an improved version of the broken RAG1 gene in the DNA of those stem cells. This is possible with a special, non-sickening virus. The repaired cells were returned to the baby through an IV. They now make a well-functioning immune system from his bone marrow. “A pediatrician who knows nothing about his history will see no difference with a healthy baby’s immune system,” says Lankester.
There is a small risk of the enhanced gene landing incorrectly and turning on a cancer gene. “But that chance is very small,” says Staal.
A pediatrician who knows nothing of his history will see no difference with a healthy baby’s immune system
Against two other forms of SCID, other research groups have developed a stem cell gene therapy. Last year British and American researchers published the results of such a treatment in fifty babies with ADA-SCID. “Great results,” says Lankester. “But the company decided to stop because it is not profitable enough.” SCID is a rare disease: every year three children are born in the Netherlands with SCID, at most one of them with RAG1 SCID.
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Staal and Lankester are working together with other European hospitals to be able to treat more patients for their research.
A number of types of gene therapy are now available, often at exorbitant prices, sometimes up to $2 million. Staal and Lankester are looking for ways to make the treatment available at an acceptable price. “You don’t want to spend 20 years working on a treatment that ends up being too expensive to use.”