"Bubble Boy" disease aided by advances in gene therapy: shots

Sometimes, rare diseases can allow scientists to launch bold new ideas. This has been the case with a disease that strikes fewer than 100 babies a year in the United States. These infants are born without a functioning immune system.

The disease is called severe combined immunodeficiency or SCID. "It was made famous in the mid-70s when the" Bubble Boy "was featured in a documentary, and I think it captivated the imagination of many people," said Matthew Porteus, pediatrician at Stanford University.

David Vetter was the boy who spent most of his short life in a plastic bubble to protect him from infections. He died at the age of 12 in 1984.

All babies born in the United States are now screened for this condition and the current best treatment – a bone marrow transplant – is used successfully more than 90% of the time. The disease remains a source of great interest for researchers.

"This is one of those diseases in which there are probably more doctors and scientists studying the disease than patients who have it," Porteus said.

In the 1990s, European scientists even cured the SCID in some patients, using a technique called gene therapy. This process involves removing defective blood cells from a patient, inserting a new gene with the help of a virus, and then putting the cells back into the body. These cells then develop the patient's immune system.

At first, this treatment in the 1990s and early 2000s seemed really promising.

"Of the 20 patients, they all had immune recovery," said Donald Kohn, an immunologist at UCLA's Center for Regenerative Medicine and Stem Cell Research. "But with time, five of them have developed leukemia."

He says that 18 of these original patients are still alive today, but the incident has put an understandable veil over the entire field of gene therapy.

Scientists went to work on how to inject new genes into cells without causing leukemia, a cancer of the blood cells. And they think they have succeeded.

Since then, gene therapy has gradually improved. The last advance, reported in the New England Journal of Medicine Wednesday, details a study of eight infants with a type of SCID called SCID-X1.

The gene that corrects the problem has been inserted into a modified version of HIV, the virus that causes AIDS. This artificial virus can not cause AIDS and has been modified to reduce the risk of triggering leukemia.

Gene therapy has been used successfully over the last decade. Scientists at the St. Jude Children's Research Hospital in Memphis have modified the treatment procedure for SCIDs by giving infants a short chemotherapy before introducing the new gene. This helped the new cells to settle down permanently. Babies have developed apparently healthy immune systems, according to the new study.

"I am delighted to see these remarkable results," said Ewelina Mamcarz, transplant specialist and first author of the new document.

"Being able to see these babies in my clinic now as toddlers is very rewarding," she says. "They live a normal life, they are no different from my daughters." Two other infants have been treated since the publication of the document, said the team.

The standard treatment for SCID is a bone marrow transplant. But this procedure often only restores a part of the child's immune system. As a result, patients must receive monthly infusions of antibodies called immunoglobulins. Jennifer Puck, pediatrician at UC-San Francisco and collaborator of the latest study, explains that infants benefiting from gene therapy do not need this drug.

These kids "grow up normally, they catch colds like everyone else and they catch infections – so I would say it's a cure," Puck says.

Of course, she adds, they will be carefully monitored for signs of leukemia and see if the effect of the therapy fades.

In his view, the key to treatment is to find these children early – through neonatal screening – before they begin to contract life-threatening infections. Screening of SCID is now conducted in the United States, although its introduction has been gradual and progressive.

Before screening was introduced, these children presented themselves at the hospital with life-threatening infections, "and we now see happy and puffy newborns who just look perfectly normal. and are never sick, "says Puck. "Sometimes their families do not understand how deeply their immune system is affected."

St. Jude's hopes to market his treatment. He has an exclusive license agreement with Mustang Bio to develop a product. A similar treatment, called Stremvelis, has already been approved by the European equivalent of the Food and Drug Administration. It targets a different mutation that causes the SCID, but the technique is very similar, including the brief dose of chemotherapy.

This latest advance is not only encouraging news for these rare patients. SCID is a test for all scientists working to develop better gene therapy techniques.

For example, instead of inserting a healthy gene into blood cells, Matt Porteus of Stanford used a precision gene editing technique called CRISPR to correct genetic error in blood cells. SCID from people. It works in the lab, "and it really opens the door to a clinical trial, hopefully in the next 12 to 18 months," he says.

All this makes the decline of leukemia in the 1990s look like a memory that erases itself. Kohn, from UCLA, says that for more than a decade, the field of gene therapy was a dead end.

It is clear that he has made his return and has treated other rare diseases, including adrenoleukodystrophy, a neurological condition better known as "Lorenzo's disease", according to a 1992 film starring a boy with the disease and seeking a cure by his parents.

Now, with continued progress in treating DICS, "it's nice to see another success for gene therapy," says Kohn.

You can contact NPR Scientific Correspondent Richard Harris at [email protected].