A doctor inspects frozen T-cells in the lab in Philadelphia, Pennsylvania, U.S. (Photographer: Bradley C. Bower/Bloomberg)

‘Bubble Boys’ Cured in Medical Breakthrough Using Gene Therapy

(Bloomberg) -- An experimental gene therapy has cured eight infants with the so-called Bubble Boy Disease, an immune-system deficiency so severe that children with it were at one time kept in total isolation for fear that even a simple common cold could be deadly. 

In a major scientific breakthrough, researchers at St. Jude Children’s Research Hospital in Memphis have developed a one-time, personalized treatment used to correct the genetic defect and build fully functioning immune systems in infants with the condition, formally known as as X-linked severe combined immunodeficiency, or SCID. 

The boys, all toddlers now, have been released from the protective isolation units that dominated their early lives and are able to play like other children their age, said Ewelina Mamcarz, an assistant member of St. Jude’s department of bone marrow transplantation. 

“We believe that the patients are cured,” Mamcarz said. “They’re living normal lives, and they have normal, functional immune systems that aren’t any different from yours and mine. They are home, some have started daycare, and they are making antibodies in response to vaccines just like we all do.”

The results involving the first eight boys to receive the treatment, to be published in the April 18 New England Journal of Medicine, are part of a new wave of experimental gene therapies that holds out the promise of cures for an array of inherited diseases, including rare conditions like spinal muscular atrophy and more common ailments such as sickle cell anemia and hemophilia. The aim is to correct defects causing disease at the most basic level by giving patients a functioning copy of a previously missing or defective gene that will live and work indefinitely inside their bodies.

Nearly two decades ago researchers from France and Italy used a similar approach to successfully treat SCID, though about one-third of the patients eventually developed leukemia, starting about a year after treatment. This time, there is no evidence of leukemia in any of the patients treated, said Stephen Gottschalk, chair of bone marrow transplantation at St. Jude.

‘Bubble Boys’ Cured in Medical Breakthrough Using Gene Therapy

“We are very close to that dream, that we have a fix, which is not partial but a complete fix for these babies,” said Avni Joshi, a pediatric infectious disease specialist at the Mayo Clinic in Rochester, Minnesota, who wasn’t involved in the study. “The risk for leukemia seems minimal, but a little longer follow-up seems warranted. I will be completely convinced when we have three to five years of follow up.”

St. Jude licensed the therapy to Mustang Bio Inc., a small biopharmaceutical company that intends to file for global regulatory approval of the gene therapy based mainly on the current data by the end of 2021. Mustang Bio Chief Executive Officer Manny Litchman said he’s confident the FDA will grant approval pending confirmation of the results in a handful of additional patients. 

“The data are extraordinary for every single patient,” Litchman said. “It’s that compelling nature of the data...that we believe will convince the FDA” to green light the treatment. 

Shares of Mustang Bio rose more than 400 percent to $13.75 in late trading. They were down 9.5 percent this year through Wednesday’s close. 

Ja’Ceon Golden, born in Las Cruces, New Mexico in 2016, was among the first boys treated with the gene therapy. His condition was discovered early, thanks to newborn screening. That hardly made the news any easier for the family.

“They told me what he had, and I asked what is that,” said his great aunt, Dannie Hawkins, 54, who is also Ja’Ceon’s guardian. “They asked: did I see ‘The Boy in the Plastic Bubble?’ I said yes. And they said that’s what he has.”

“The Boy in the Plastic Bubble” was a 1976 made-for-TV movie featuring John Travolta that was inspired by the life of David Vetter. He was born in Texas in 1971 with severe combined immunodeficiency and survived for 12 years thanks in part to the sterile chamber that he lived in, keeping germs at bay, initially in the hospital and later for brief periods at home.

‘Bubble Boys’ Cured in Medical Breakthrough Using Gene Therapy

For decades, Vetter’s poignant story represented the plight of children with the disease. The ailment almost always strikes boys rather than girls. 

“Because infants with the disorder have no functioning immune system, without treatment a diagnosis of SCID is truly a death sentence,” Mamcarz said.

J’aCeon’s future looks a lot more bright. He was flown to the University of California, San Francisco’s Benioff Children’s Hospital, which collaborated with St. Jude on the study. 

Step one in Ja’Ceon’s recovery was removing his bone marrow cells and sending them to St. Jude in Memphis. Researchers had previously taken a powerful virus, similar to one that can cause HIV, and stripped it of any infection-causing potential. Then they inserted normal copies of the IL2RG gene inside the pared down viral particles, making them potent gene delivery devices.

The researchers then combined the viral particles with the stem cells from Ja’Ceon’s bone marrow. They nurtured the mixture until the virus penetrated the cells and deposited the functioning gene, then froze and shipped them back to UCSF. Meanwhile, Ja’Ceon was given low-dose chemotherapy to make room for the new cells. The gene therapy was infused into Ja’Ceon in a procedure that took just a few minutes. Within months, the healthy genes had taken hold and he had a fully functioning immune system. He was released from the hospital in May 2017, when he was about eight months old.

“He was able to go out into the free world,” Hawkins, his aunt, said. “He had never been out of the hospital, since birth.”

The real test, though, was when Ja’Ceon picked up bugs just as any baby will. He was hospitalized twice for three days due to different infections and each time he fully recovered. Scary as the infections were, they helped Hawkins realize that Ja’Ceon, now a rambunctious two-and-a-half year old with – she swears – a mean curve ball, is fundamentally healthy.

“Even now, he’ll catch a cold and I will feel panic,” she said. “But then I remind myself that he’s a normal kid and he’s going to go through these things now.”

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