Doctors develop "treatment" for babies with "bubble boy" disease

Severe Combined Immune Deficiency or SCID refers to a group of rare diseases caused by mutations in genes that influence the development and function of important immune cells. Infants born with SCID may appear healthy but are very susceptible to serious infections – to the point that a cold could kill them.

Because of Hollywood's fascination with the disorder, many people might think of SCID as the disease presented in the 1976 John Travolta film "The Boy in the Plastic Bubble" or in the 2017 film "Everything , Everything ", featuring Amandla Stenberg.

Yet, some misconceptions about the disease have been portrayed on the big screen, and living in a plastic bubble or locked inside your home – as in these movies – has never been a standard treatment for the disease, according to the Foundation for Immune Deficiency. .

A bone marrow transplant is usually used to treat SCID early in life, before an infection can occur, and transplants in the first three months of life have the highest success rate. Paired sibling transplants are preferred, but in the absence, a parent or unrelated donor may be involved. Although transplants save their lives, they often only partially restore the patient's immunity.

Now, it turns out that there is another way to treat the disease – and doctors call this new therapy a "cure".

A team led by researchers at the St. Jude Children's Research Hospital in Memphis has developed an experimental gene therapy that involves harvesting bone marrow stem cells from a child with SCID-X1, inserting in these cells the normal gene missing in these patients. reinject them back into the child so that the cells repopulate and restore the immune system.

It's complicated but it raises eyebrows in the medical field.

There are several types of SCID, depending on the defective gene involved. Mutations of the IL2RG gene on the X chromosome cause X-linked SCIDs or SCID-X1s, which mainly affect young boys. According to the National Library of Medicine of the United States, the disease probably affects at least one newborn from 50,000 to 100,000.

Doctors say that if he is not treated, a child with SCID-X1 will rarely live beyond his second birthday. In the United States, all newborns are screened for SCID.

"From a physiological point of view and a" quality of life "for these patients, it is a cure. The question will become: will it be a treatment Will it last 10, 20 or 50 years for these children? Only time will tell, "said Dr. James Downing, President and CEO of the Children's Research Hospital on Tuesday. St. Jude,

"This is the first time we have seen a complete rebuilding of the immune system, which has allowed these children to come out of their isolation," he said. "So we are comfortable, I think, at this point, stating that it is a cure, only time will tell if this treatment will be sustainable and for life." "

Recently developed gene therapy, combined with chemotherapy called busulfan, has been described in a study published Wednesday in the New England Journal of Medicine.

Ja & Ceon and Omarion both participated in a clinical trial to test the treatment, which has been shown to be effective in the treatment of SCID-X1 in both cases.

"Children are cured because, for the first time, we have been able to restore the three types of cells that make up the entire immune system," said Dr. Ewelina Mamcarz, first author of the study and researcher at St . Jude. .

The treatment restored healthy functioning in various groups of immune cells, including T cells, B cells, and NK cells.

"We will continue to follow these patients, but the result is simply that these patients have a complete restoration of their immune system without immediate side effects," Mamcarz said.

"As this therapy is still in the early stages of development, it is too early to estimate the overall cost, but we want it to be accessible to all children who need it," she said. "Most patients only need one infusion and, as we were able to completely restore their immune system, they did not need additional treatment, as at one time." graft."

"He had never been out of the hospital before"

When Ja & Ceon Golden was born in New Mexico in 2016, he never had the chance to come home from the hospital. His screening tests in the newborn showed that he was suffering from SCID-X1. When the doctors informed her aunt, Dannie Hawkins, of the results of her test, she did not know what to think.

"I told myself" Well, what is it? "And they answered me," Well, have you ever seen the movie "The boy with the bubble"? And I was like "yes," and they replied, "well, that's what he did." At that time, all sorts of things were going through my mind, "Hawkins told CNN exclusively.

Hawkins, Ja? Ceon's tutor, learned more about the disorder and how to take care of Ja & Con during his stay at the hospital, including constantly washing his hands in order to do not expose it to germs, and heating the water before its baths for the water was sterile.

The doctors then told Hawkins that she could travel to San Francisco to receive treatment against Ja? Ceon, and she was informed of the study on new gene therapy.

In 2017, while he was in San Francisco, Ja? Ceon was treated for his illness. As soon as Hawkins learned that the treatment had been successful, she took Ja 'Con out for the first time.

"It was very nice to see him smile and watch, because he could only see the cars by the window, etc., because I was putting him at the hospital window for that." He can see people walking and letting the cars go by, "she says. "Just to see him look at the cars and smile, it was a blessing."

In the days that followed, Hawkins was still worried about whether his nephew's immune system was fully restored.

"I still had this fear of," And he gets sick? "You know, because he had never left the hospital before," did he? she declared.

Then, "we went to a Giants game, and his immune system was able to handle that, with everyone present, and that's when I realized it was working," he said. she said.

At the game, Hawkins took baseball fan Ja? Ceon to meet Barry Bonds, a former San Francisco Giants star. Aside from Hawkins and a health professional, he was the first to hold Ja? Ceon.

"He has never known Ja? Ceon's condition because it's not something I've talked to him about, but he has to hold it in his arms and we've took pictures, "said Hawkins. "It was the third day of the hospital."

"I was really praying for a miracle, and I think that's what happened …"

As for Omarion Jordan, he is now a healthy, adorable and healthy child, but that has not always been the case.

When Omarion was born almost a year ago in Indiana, the state did not test the newborns for SCID and his family was not at home. current of his condition. As a child, he often had health problems, such as rashes or scaly patches on the skin, but nobody knew why.

"They were sort of guessing what was wrong, like they told me that he had a cradle, he had eczema, he had an allergy to milk," he said. declared his mother, Kristin Simpson.

"I felt like nobody took me seriously and that it was much more serious than anyone would let them," she said.

One day, Simpson had enough. She took her son to see his primary care pediatrician, who then sent Omarion to a nearby hospital.

At the hospital, "they said that he was suffering from pneumonia, that he had a viral infection, that he was having a fever, that he was having trouble breathing and that they continued to do more and more tests, "Simpson said. "Then I remember that they told me that he had a SCID related to X."

Omarion was about 3 months old and Simpson had never heard of this disorder.

Once Omarion was diagnosed, Simpson and his doctors made efforts not to expose him to germs, and he was prevented from going out for months. He was then enrolled in the study on the new gene therapy.

Afterwards, Simpson was told that his son had been successfully treated.

"Frankly, I honestly waited for the worst," she said.

"I was really praying for a miracle, and I think that's what happened … I do not think it's anything less than a miracle," she said. . "As soon as we found out that he was cured, he was taking a nap, and we woke him up to get him out, and then we stayed out all day until that day. that he's falling asleep. "

What's next for gene therapy

Ja & # 39; Ceon and Omarion were two of eight infantile patients involved in the new study. Patients, mean age 3½ months and newly diagnosed with SCID-X1, were treated with gene therapy.

The therapy involved the collection of stem cells in the bone marrow, and then using a virus as a vector to insert a healthy copy of the IL2RG gene into patients' cells before reinjecting those cells back into their bodies. "The process takes about 10 days," she said.

"Before reinjection of gene-corrected gene stem cells, infants received two days of low-dose busulfan, the most commonly used chemotherapy agent in bone marrow transplants, to free up space in the cells. Donor strains The result is truly exceptional for our patients, "said Mamcarz.

The vector used in the therapy was an artificial copy of the human immunodeficiency virus, or HIV, but patients "can not be infected with HIV," said Dr. Morton Cowan, a pediatrician at the University of Toronto. University of California San Francisco. was an author of the study. "It's causing HIV, but it's no longer really HIV when it's inserted," he said. The virus has been designed so that its active parts are eliminated, making it safe to use.

"This virus is able to efficiently deliver the healthy copy of the gene in stem cells in a way that was not possible before.We believe that this type of virus is safer and more effective for gene therapy. "said Dr. Stephen Gottschalk, chair of the Department of Bone Marrow Transplantation and Cell Therapy at the St. Jude Children's Research Hospital and author of the study, announced Tuesday.

Such gene therapies may also present a cancer risk, since the introduction of the IL2RG gene into the cells of one patient could affect adjacent genes, but Gottschalk said the HIV vector was designed to include insulators that block the activation of surrounding genes.

"The goal is to prevent gene therapy from inadvertently causing leukemia," he said.

According to the study, all patients survived treatment and were well on average 16.4 months after treatment, but further research is needed to determine whether the effects will continue with aging patients.

Researchers are studying how this gene therapy could be used to treat elderly patients and with other types of diseases.

For example, "the same vector that was made here in St. Jude is currently being used by the National Institutes of Health to treat older children who have had an unsuccessful bone marrow transplant," said Mamcarz.

"We are exploring other immune deficits, but this vector could also be used to treat sickle cell disease, a life-threatening blood disease that is very common worldwide," she said.

CNN's Nadia Kounang contributed to this story.