The real bubble boy

Dec. 12, 2013— — Heather Smith carries a recessive gene for a rare sex-linked primary immune deficiency disease that kills most boys before they are 1 year old, and she passed it on to her two sons.

Her oldest, Brandon, behaved like a normal, healthy baby until he was about six months old and couldn’t fight off his first cold. He had trouble eating, he developed a rash on his face and thrush in his mouth, and his fingernails turned blue.

‘Bubble Boy’ legislation to create home treatment program

Brandon died within three weeks of being hospitalized in 1993 of severe combined immunodeficiency, or SCID-X1, commonly known as “bubble boy disease.” It was so named for David Vetter, a Texas child with SCID-X1, who died in 1984 after living for 12 years in a germ-free plastic bubble.

“I had seen the movie with John Travolta, but I never dreamed I would someday lose my first-born child to this devastating disease,” said Smith, founder of SCID-Angels for Life, which successfully pushed for mandatory screening of all newborns for the disease in her home state of Florida.

” wasn’t even an option presented to us for consideration,” she said. “Instead, we were told that we had to say goodbye to our only child and turn off the machines.”

After genetic testing, Smith’s son Taylor was born in 1995, and because of early detection, he received the first-ever in-utero bone marrow cell transplant, previously only done on sheep. Today, at 18, he is “thriving,” according to his mother and leads a normal life. He’s now preparing to go to college.

Taylor receives infusions of gamma globulin, a blood product that helps his immune system fight off infection.

“It’s a treatment, not a cure,” Smith, 45, told ABCNews.com. “He will take it for the rest of his life. He still has a defective gene.”

But now, an international consortium of scientists has perfected gene therapy in promising clinical trials that they say may lead to an eventual long-term cure for SCID-X1.

Eight out of nine children given gene therapy in the study — all age 3 and younger and living around the world — fighting off everyday germs that once might have killed them. They have been cancer-free for between nine and 36 months.

“These boys are basically born without any immune system and are not able to fight off even a cold,” said Dr. David A. Williams, a pediatric hematologist/oncologist who directs the gene therapy program at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center.

The U.S. study sites are Dana-Farber/Boston Children’s, Cincinnati Children’s Hospital and UCLA. They are being funded by the National Institute of Allergy and Infectious Diseases and the National Heart Lung and Blood Institute’s Product Assistance for Cellular Therapies Program.

The standard treatment for boys with SCID-X1 is stem cell or bone marrow transplantation. That works well when there is a sibling who matches or if it’s done before a child contracts an infection.

But problems happen graft versus host disease develops and the incoming immune system attacks the child’s own cells, or when the graft just doesn’t take.

“This is the potential advantage in the experimental trials,” said Williams. “Since you are using the child’s own cells, there is no search for a donor. The child is its own donor.”

Gene therapy works by taking stem cells from the child’s own bone marrow, correcting the IL-2 common gamma chain receptor gene, then reintroducing the cells back into the child.

There, the genetically engineered stem cells multiply and produce normal immune cells.

Heather Smith said she was hesitant to “take a risk” and consider gene therapy for Taylor in the future, even if he were a good candidate.

“Other than getting infusions every three weeks, he feels like he lives a totally normal life,” she said. “His quality of life is so good.”

But for other young children down the road, she said, “it’s extremely exciting if this leads to a cure.”

An estimated 250,000 people in the United States have one of the 185 primary immunodeficiency diseases, according to the Immune Deficiency Foundation.

There are several forms of SCID, but the most common type is linked to the X-chromosome and affects only males. Unlike boys, who have a Y chromosome, girls have a second X chromosome that is able to function for the faulty one.

Boys with SCID-X1 have a severe defect in both the T- and B-lymphocyte systems, causing serious and sometimes life-threatening infections within the first few years of life, including pneumonia, meningitis or bloodstream infections.

In two previous gene therapy trials in Paris and London, 18 of the 20 boys had a complete repair of their immune system, according to Williams, but five developed cancer as a consequence of the virus vector used to deliver the “payload” of repaired gene.

As a result the Food and Drug Administration stopped the trial for child patients in the United States. But in the latest trial, based in Germany, Britain and the United States, scientists “fished out where the vector landed and saw that it was next to a gene that was oncogenic (cancer-causing),” said Williams.

Now, they have changed the virus vector to deliver the repaired gene more safely.

“The bottom line is the vector seems to work as well as the old vector,” he said. “We have to wait longer to know whether any of the children develop leukemia before we can say for sure.”

The two children who have been in the study the longest have been cancer-free for more three years, which is about the point those in the previous studies had developed the cancer.

The findings of the Dana-Farber/Boston Children’s study were presented this week at the annual meeting of the American Society of Hematology in New Orleans by pediatric hematologist/oncologist Dr. Sung-Yun Pai.

She treats 6-year-old Aidan Seymour of Springfield, Mass., who was diagnosed with SCID-X1 at the age of seven months. At the time, gene therapy was not available, so he underwent a successful blood cord transplant, which can be done with an unmatched donor. In order to minimize the risk for graft versus host disease, he had chemotherapy first.

“We had hope, but there was risk,” said his mother, Kirstin Seymour, 37. “It is an art, not a science.”

At the time, a cord transplant seemed the best option.

“I can say as a parent, that if I had had that opportunity for gene therapy, 100 percent it would probably have been my course of action,” she said.

Today, Aiden is doing well and takes no medications, but Seymour worries about whether Aidan will ever be able to have children or if he will develop a secondary cancer because of chemotherapy.

“At this point, they say he should be able to live a long, happy, healthy life like everyone else,” said Seymour.

But Aidan can never get a second transplant from the blood cord donor because of the anonymous nature of the transplant, so gene therapy might provide promise for him.

“It allows the body to cure itself from its deficits, and that is pretty amazing,” said Seymour.

Williams is also optimistic about the research.

“Because this is very experimental in human beings, we can’t answer if these children are cured with any surety yet,” he said. “But because we put the correction into the blood stem itself and those stem cells last a lifetime, it is likely a long-term correction of the child.”

Gene therapy technology may also help children with other genetic diseases, most notably sickle cell anemia.

“One of the great things about this trial is that it has multiple institutions around the world working together,” Williams said.

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The Boy in the Bubble | Article

David Vetter’s Sister

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Carol Ann holds Katherine while baby David is in the background | Patricia Bealmear PH.D.

Katherine Vetter was almost four years old when her brother David was born with an immunodeficiency disorder. The close genetic match between siblings meant that Katherine was David’s best hope for a cure at the beginning and at the end of his life.

Not a Match
The doctors at Texas Children’s Hospital hoped that Katherine’s bone marrow, the production center of white blood cells in the human body, could be transplanted into David’s system and create a working immune system. Unfortunately, the siblings’ marrow was not a perfect match and the transplant could not be performed. David spent the rest of his twelve years of life in plastic isolator bubbles at the hospital and at home.

Balancing Act
When David was at home, he naturally required more attention than his sister. Their mother, Carol Ann, recalled that when Katherine was outside while David required attending, “I would volley back and forth to watch them both, and it got pretty frustrating. I’d say a little prayer every time Katherine was playing outside: ‘God, I’ll take care of David if you’ll watch over Katherine.'” At least one doctor worried about the “emotional deprivation” of Katherine “if the parents choose to invest all of their emotional capital in their packaged child.”

Protective Sister
Despite the physical barrier, the siblings were close. Katherine slept in the living room next to the bubble every night David was at home, until she became an adolescent. When strangers gawked at David in his transport bubble, Katherine would shield her brother from the unwanted attention.

Sibling Fights
Of course, as siblings, they also fought. Katherine called David a “brat” and he called her a “dummy.” They even had physical fights, although they didn’t last long. Their mother remembers an instance when David, using the rubber gloves that communicated through the bubble, punched Katherine. Before she could retaliate, he had scooted to the far corner of the bubble where she couldn’t reach him. Other times, the rubber gloves that allowed access into the bubble were used for shoving matches.

Ultimate Control
Katherine always had the upper hand, though. If they argued — over what television program to watch, say — she would threaten and then actually unplug David’s bubble (if his play area deflated, he still had other rooms that he could seal himself into). David would plead, “plug me back in,” and she always did, having won the argument.

Reminder of Limits
Their physical interactions were unique, but they had an emotional bond similar to any other brother and sister. Still, Katherine’s outside life must have been a constant reminder to David of his own limited world. After his sister announced that she was going out to have hamburgers with a friend’s family, one academic paper reported, “D jumped up shouting, ‘I want to go too.’ Within seconds, however, he stopped very abruptly, stepped back, and said softly, ‘No I don’t.'”

A Gift of Hope
By 1983 research in bone marrow transplants had advanced to the point where donors did not have to be exact matches to recipients. There was new hope that David might be able to receive his sister’s bone marrow, generate an immune system, and leave his protective environment. After the entire family discussed the procedure, the teenaged Katherine had her marrow extracted in Boston. Doctors treated it and then flew it down to be donated to David. That Christmas, as a thank you gift, David gave Katherine a sapphire and diamond ring that their mother had helped pick out.

Out of the Bubble
Sadly, Katherine’s gift of bone marrow — her brother’s only hope for a cure — would bring about his end. David unexpectedly got violently ill for the first time, and had to be removed from the bubble. Katherine and her parents were there when he came out. He died two weeks later. An autopsy revealed that David had died of cancer, a complication of the Epstein Barr virus which must have been inadvertently transmitted through Katherine’s bone marrow.

Today
Katherine is now married with two young sons of her own. She expressed the hope that they may one day attend The David Elementary School, named after her brother. “Little David, even though he’s gone, still lives on,” she said.

From the Mother of the ‘Bubble Boy’: His Short Life Left a Long Legacy

By Carol Ann Demaret, Special to Everyday Health

My beloved son David was born in 1971 with severe combined immune deficiency (SCID), the most serious type of primary immunodeficiency disease.

In a person with SCID like David, there is an absence of T-cells and, as a result, B-cells, the specialized white blood cells made in the bone marrow to fight infection, don’t function.

These genetic defects cause extreme susceptibility to serious illness, and the body cannot fight infections. When David had SCID, very little was known about the disease, and a bone marrow transplant from an exactly matched donor was the only cure for the disorder, but there was no match available in our family.

NASA Steps In to Save My Second Son

Our older son had passed away from this disease, so we were on alert when David was born. Doctors diagnosed his condition when he was just two weeks old — much more quickly than most children with SCID at that time. That saved his life, but to keep him from being infected with the many bacteria and viruses that could kill him, David had to live in a completely germ-free environment.

We were fortunate that NASA offered to construct a sterile space for David to live, inside a plastic “bubble” that was set up for him both at the hospital and in our home in a suburb of Houston. They also built a spacesuit for David that is now part of the Smithsonian’s collection. He grew up surrounded by media attention but never being able to be touched by those who loved him.

A Bone Marrow Transplant Leads to Lymphoma

We were always open and honest with David and explained his disease to him. As he got older, he understood that because of his disease, he had to wait until science found the right treatment for him to leave his sterile environment. By the time he was 12, bone marrow transplants were becoming more advanced, and doctors felt this was a viable option for David. While not a perfect match, our daughter was deemed an acceptable blood marrow donor, and we proceeded with the operation.

Unfortunately, a viral infection was transmitted during the transplant and this caused David to develop lymphoma. He died on February 22, 1984, at the age of 12. The only time I could touch him was as he was dying — wonderful and heartbreaking at the same time.

David’s Life Gave Life to Others

I believe that God had a divine plan for David. His life, however short or restricted, helped scientists learn more about primary immunodeficiencies so that they could help other infants with SCID. That’s given our family enormous comfort over the years and helped us manage our great sorrow.

Dr. William Shearer, David’s physician at the time, and now a professor of pediatrics and immunology at Baylor College of Medicine, has often said that the knowledge gained from treating David not only helped the thousands of children born with SCID but also contributed to medical knowledge about treating AIDS, viral infections and cancer.

We were so grateful to Dr. Shearer, who was extremely invested in finding new options for children like David. He also was instrumental in informing pediatricians and the public about SCID. Without him, who knows where we would be today in understanding SCID and other primary immunodeficiency diseases, both genetic and acquired?

SCID Newborn Screenings Still Not Available in Many States

When David was alive, I prayed that no other child would have to experience life inside a bubble. And medical advances have answered my prayers. Today, a simple, inexpensive newborn screening test can detect SCID in newborns — in time for the babies to be treated. However, many states have not adopted this screening test, despite the fact that the U.S. Secretary of Health and Human Services recommended in 2010 that SCID screening be part of national infant screening guidelines.

If a baby with SCID is screened, diagnosed and treated early, generally within several months of birth, there is more than a 90 percent chance that the child will be effectively “cured.” Without treatment, a baby will most likely die. When SCID is detected early, patients have an expanding number of options that include bone marrow transplants, gene therapies or enzyme replacement therapies. It’s also cost-effective to detect SCID with a screening test. Each child who is treated early represents approximately $500,000 in savings to the healthcare system.

Looking Forward to Better Care for Immune Deficiency Diseases

I give as much time as I can to the Immune Deficiency Foundation (IDF) where I serve on the Board of Trustees, and to The David Center in the Texas Children’s Hospital, named for David. IDF provides education, advocacy and empowerment to the thousands of people with primary immunodeficiency across the country, and The David Center cares for children with immune, allergic or rheumatic disorders.

We now know that there are more than 200 types of primary immunodeficiency diseases, which can occur in any decade of life. Although varying in severity, most result in increased susceptibility to infections, so early diagnosis and treatment is critical. If you or your child has primary immunodeficiency, I encourage you to learn more at the IDF website. You are not alone, and there is a whole community and a strong organization to support you regardless of where you live. Learn more about the IDF SCID Newborn Screening Campaign. I urge everyone to push for SCID screening in their state — it will save lives.

David’s life showed courage, patience and understanding. He accepted the unique circumstances of his life but waited to find the way to come out of his bubble. We prepared him to be able to socialize and eventually join the outside world. Unfortunately, that never happened.

However, I know David’s brief life was meaningful every time a mother tells me that her baby would not be alive today without David. That is the best gift that he, or anyone, could give the world.

Carol Ann Demaret is the mother of David Vetter, affectionately known to the world as “The Boy in the Bubble” because he lived inside a protective plastic isolator for 12 years to prevent him from contracting life-threatening infections. She reflects on how her son’s short, confined life has provided freedom and longevity for so many others with primary immunodeficiency diseases.

Photo Credits:

Top: Texas Children’s Hospital

Middle: Baylor College of Medicine Photo Archives

Bottom: Baylor College of Medicine Photo Archives

‘Bubble boy’ David Vetter receives bone marrow transplant in 1983

From time to time on this broadcast and others you hear us refer to medical breakthroughs. Tonight a medical report which could literally mean breaking through a plastic shell that has surrounded a young boy for his entire life. David the boy suffers from a complete inability to fight any kind of infection. Here’s ABC’s George street. For twelve years David has been living in this plastic bubble this germ free environment waiting for medical breakthrough to set him free. And it appears his weight may be over just before dawn this morning his doctors performed a radical new kind of transport. Okay we’ll see. A grown our planet. And Teixeira. Then head on especially for giving it to around. They need you now. Any compatible. Move compatible. Fourteen. David needed a bone marrow transplant because since birth his Merrill has not produced enough white blood cells to fight off invading germs. He had no immune system which meant even a mild cold could be fatal. A bone marrow transplant would cure it but an exact Max for David’s bone marrow could not be found in anything short of an exact match. Would lead to a type of rejection called a graft vs host disease. Also fatal for two years doctors at the Dana Farber Cancer Institute in Boston. Have been experimenting with monoclonal antibodies a substance that can seek out and destroy the specific cells that caused this rejection. These month olds will allow us to destroy the cells which caused graft vs host disease which is being seen your limitation. To transplanting. One individual into another. Geneva vegan three other immune deficient children like David have already been cured with these monoclonal antibodies. Because of those successes David’s parents agreed to try using marrow from his sister. Doctors say it will be at least ninety days before they’ll know if the transplant worked but now for the first time in twelve years David and is firmly dare to hope. George Strait ABC news.

The grimly named “isolator” was supposed to be temporary.

Everyone expected that the baby boy named David Vetter would develop a functioning immune system once he received a bone marrow transplant from his sister. Then he could leave the plastic walls that protected him from germs and live happily ever after, forever able to touch those he loved.

It was not to be. As a fascinating and heartbreaking new television documentary reveals, overly optimistic doctors and modern medical technology would fail the “boy in the bubble.” Doomed by a deadly combination of hope and hubris, he wouldn’t make it to his teen years.

While his name has fallen into obscurity, Vetter was a celebrity of sorts in the 1970s and early ’80s. In The Boy in the Bubble, which airs Monday night as part of PBS’ American Experience series, we see him live his entire life behind plastic, touched only by black neoprene gloves sticking through the walls of his bubble.

In their defense, a team of Houston medical experts didn’t have any other way to save Vetter’s life. They rushed him into his bubble immediately after his 1971 birth in a special germ-free operating room, correctly assuming he suffered from a rare inherited condition called severe combined immunodeficiency.

The experts also assumed they could cure him, and they made no plans for what to do if they couldn’t. Even now, none of the three members of the team seem to harbor any serious regrets; amazingly, each eventually abandoned Vetter and went on to another job.

When the bone marrow transplant failed, Vetter stayed in the bubble, waiting for a cure, even as a growing chorus of critics wondered if he belonged there. He grew older, wearing Star Wars T-shirts and learning in amazement about such real-world wonders as falling leaves.

The cure never came. But as the documentary vividly reveals, plenty of nightmares did. An increasingly unstable Vetter became obsessed with the danger of germs, so petrified with fear that he couldn’t handle brief forays into the outside world in a NASA-designed space suit. But his parents refused to let him out of the bubble to face near-certain death.

Vetter died in 1984 at the age of 12 after a failed operation that forced him out of his bubble. Now, Vetter’s disease is treatable 90 percent of the time. And for those who can’t be treated, there’s no bubble option: The germ-free isolator is gone for good.

See related slideshow

But over time, his life came to be fraught with ethical dilemmas. For instance, what if a mature David at some point demanded freedom from his hermetic environment, regardless of the risk? A psychologist who worked with him has recounted how the boy, always cheerful in televised images, sometimes raged off-camera at the terrible hand fate had dealt him.

In October 1983, his doctors tried a new bone marrow technique, one that did not require a perfect blood match. As had originally been planned, Katherine Vetter was the donor. At first, the procedure seemed to work. But dormant and undetected in Katherine’s marrow was a virus, Epstein-Barr. It proved to be a killer, the trigger of cancerous tumors that overwhelmed David’s body.

At long last, he was taken out of the bubble and treated in a sterile hospital room. For the first time in his life, he was able to receive that most primal of human contacts: a mother’s kiss. But the end was at hand. On Feb. 22, 1984, two weeks after leaving the bubble — with a wink to his doctor, William T. Shearer, as a final gesture — David died.

Since then, medical science has progressed to a point where a bone-marrow transplant is usually successful in treating SCID when it is done within a baby’s first three months. Early SCID detection — it can be done in utero, the Retro Report video shows — has also greatly improved.

A possible new weapon in the medical arsenal is gene therapy, still in the clinical trial stage. With a harmless virus serving as the carrier, a healthy gene is inserted into a patient’s system to do the work of a defective gene that is the source of diseases like immune deficiency, sickle cell anemia and hemophilia. Gene therapy’s healing potential is widely accepted. But it has had plenty of setbacks along with triumphs since it was first tried in 1990, and has yet to be blessed by the Food and Drug Administration. Inevitably, too, there are ethical considerations. For some people, anything that smacks of genetic tinkering can touch off Frankenstein fears about whether we are redesigning human beings.

Nor have doctors been let off the hook. The Rev. Raymond J. Lawrence, who was the director of clinical pastoral education at Texas Children’s Hospital during David’s time there, spoke at a 1975 conference that focused on the ethics of the boy’s medical care. Looking ahead to when David might reach his teens, Mr. Lawrence asked, “Could this person live for 15 years in that kind of isolation and be human?” Doctors at the conference generally responded that their obligation was to do what they could to preserve the boy’s life until they might be in a position to make it normal.

David was the last person believed to have been placed in so confined a bubble (other than in a few weak stabs at humor in film and on television). He left a legacy for science that included a new understanding of the role viruses can play in causing cancer. “What he gave us was a powerful lesson in many areas of medicine — and just in life itself,” Dr. Shearer told Retro Report.

The boy was buried in Conroe, a town he never truly knew. In noting that “he never touched the world,” his epitaph added, “But the world was touched by him.”

Opinion: The Doctor And ‘The Boy In The Bubble’

David Vetter plays in the enclosed plastic environment that he had to stay in to survive. Bettmann/Bettmann Archive hide caption

toggle caption Bettmann/Bettmann Archive

David Vetter plays in the enclosed plastic environment that he had to stay in to survive.

Bettmann/Bettmann Archive

As 12-year-old David Vetter was about to die at Texas Children’s Hospital in 1984, he gave a last wink to his doctor, William T. Shearer. His wife told us Dr. Shearer carried that moment through the rest of his life.

Dr. Shearer, a professor of pediatrics at Baylor College of Medicine, died this week at the age of 81.

David Vetter had been born with severe combined immunodeficiency, a rare disease that could have made it fatal for him to be touched, held, kissed by his parents or even take a breath of fresh air.

Doctors devised a sterile clear plastic pouch to keep David alive until medical science could come up with … something else.

David Vetter became “The Boy in the Bubble.” As he grew, it was a joy to see occasional photos of him smiling, playing, and so manifestly alive.

It was also heartbreaking to see a smiling little boy who had to live in a bubble, and wonder how long he could, or even should, live that way.

NASA engineers constructed a spacesuit for David when he was 6 that enabled him to walk around his family’s house and even play catch with his sister, Katherine. But psychologists who worked with him said David was growing bitter about the way he had to live in a bubble.

“We all knew the day would come when a decision would have to be made: in or out,” Dr. Shearer recollected for a New York Times video in 2015.

When David was 12, Dr. Shearer and his team used a new technique for a bone marrow transplant from his sister. But there turned out to be a dormant virus in Katherine’s marrow; the transplant didn’t work. For the first time since he was born, David was freed from his bubble, to be kissed by his mother, to feel the air of the world on his face and to die with that last wink.

Dr. Shearer never really let go of David Vetter. He used lessons from his care to guide him as he focused on the new epidemic of HIV/AIDS in children. And today, early screening means many children can have a bone marrow transplant before they’re even born.

“What we learned from David is a textbook,” he told the Houston Chronicle last year. “A textbook that he wrote with his life, and that we are still learning from.”

Lynn des Prez, Dr. Shearer’ wife, told us this week that they only traveled to medical conferences and that he worked seven days a week. But he also had three marriages and six children, five of whom were adopted. And, she says, he kept David Vetter’s wink in his heart.

“I like to think,” she told us, “that he has a friend up there, to show him around.”

Study: Researchers successfully treat babies with ‘bubble boy’ disease using gene therapy

MEMPHIS, Tenn. – Researchers from St. Jude Children’s Research Hospital have cured babies with “bubble boy” disease through gene therapy involving a re-engineered virus, according to a newly published study.

St. Jude performed the therapy on infants newly diagnosed with X-linked severe combined immunodeficiency (SCID-X1) – a genetic condition also known as “bubble boy” disease – according to a study published in the New England Journal of Medicine’s April 18 issue.

The disease prevents babies from developing an immune system to fight even routine infections. In January 2018, St. Jude researchers reported that babies in the trial developed fully functioning immune systems but would be monitored further to confirm its long-term benefits.

“Previous infections cleared in all infants, and all continued to grow normally,” the study said of the results.

St. Jude and UCSF Benioff Children’s Hospital San Francisco treated the children enrolled in the clinical trial with gene therapy developed by St. Jude’s Brian Sorrentino, the study’s senior author, who led groundbreaking gene therapy research before his death in November at 60 years old.

James Downing, CEO of St. Jude Children’s Research Hospital, said it was the “lifelong ambition” of Sorrentino, a survivor of pediatric cancer, to develop a cure.

“We’re comfortable, I think, at this point stating this is a cure,” Downing said. “Only time will say this will be a durable, lifelong cure.”

After the therapy, the babies received their standard vaccinations and are now living a normal life with fully functioning immune systems, St. Jude says. Ten infants have received the therapy so far.

Study co-author Stephen Gottschalk, chair of the St. Jude Department of Bone Marrow Transplantation and Cellular Therapy, said the researchers hope the therapy will be a template for treating other blood disorders.

What is ‘bubble boy’ disease?

Newborns with bubble boy disease, caused by a mutation inside a specific gene, must be placed in protective isolation because they lack a proper immune system. Contact with the outside world is a major infection risk.

Perhaps the most well-known person with the disease was David Vetter, who died in 1984 at 12 years old. He helped inspire the 1976 movie “The Boy in the Plastic Bubble.”

Most with the disease die by age 2 without treatment.

“This disease is called bubble boy disease because babies had to be kept in special plastic chambers to protect them from infections,” said first and corresponding author Ewelina Mamcarz of the St. Jude Department of Bone Marrow Transplantation and Cellular Therapy. “We don’t have these chambers now, we are more advanced, but we need to protect them from infections as simple as a common cold virus (that) can kill them.”

The patients came to researchers between 2 and 14 months of age, Mamcarz said, with “severe life-threatening infections.”

How the therapy works

The gene therapy works like this: A deactivated virus is inserted into the patient’s bone marrow, which delivers the correct gene copy into blood stem cells, replacing the defective one. These cells are then frozen and undergo testing.

“This virus is able to effectively deliver a healthy copy of the gene into a stem cell in a way that was not possible before,” Mamcarz said.

The patient then receives two days of low-dose busulfan, a chemotherapy drug that makes space in the marrow for the stem cells to grow, and the cells are then infused back into the patient.

It takes about 10 days from the time the cells are taken out to when they are infused into the patient, Mamcarz said.

The proper immune cells were found within three months of the treatment in all but one patient, who needed a second dose of gene therapy, St. Jude says.

“This novel approach has shown really outstanding results for the infants,” Downing said. “The treatment has fully restored the immune system in these patients, which wasn’t possible before, and has no immediate side effects.”

The gene therapy developed and produced at St. Jude differs from previous gene replacement efforts in part by not activating adjacent genes that could cause leukemia. The viruses are equipped with insulators to block that accidental activation.

“Past gene therapy did not have insulators, which inadvertently caused leukemia,” Gottschalk said.

Is this the definitive cure?

Current treatments for bubble boy disease are limited. Bone marrow transplants from compatible sibling donors are the best bet, but most patients lack a proper donor.

Mamcarz said researchers would like to treat more patients and follow them for longer periods of time to see if the gene therapy performed in the clinical trial can truly be used as an upfront treatment, and it’s still too early to determine costs.

But the results from the research are a first, and their approach could be used to eventually treat other disorders like sickle cell disease, she said.

“The kids are cured because for the first time, we are able to restore all three types of cells that constitute a full immune system: T cells, B cells and NK cells,” Mamcarz said. “Our patients are able to generate a healthy, fully functioning immune system. That is the first for gene therapy.”

Downing said the search for a cure has been a journey spanning more than a decade. Early gene therapy studies with the viral vectors led to leukemia, he said, causing the work to stall. But Sorrentino pushed on.

“Brian Sorrentino decided we really needed to produce vectors we could trust in not inducing leukemia,” Downing said.

The patients’ quality of life following the treatment shows they indeed found a cure, Downing said.

“The question will become, ‘Will it be a durable cure? Will it last 10, 20, 50 years for these children?’ And only time will tell,” he said.

Follow Max Garland on Twitter: @MaxGarlandTypes.

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