Researchers from St. Jude Childrens Research Hospital have cured babies with bubble boy disease through gene therapy. Angela Gosnell, Knoxville News Sentinel

MEMPHIS, Tenn. Researchers from St. Jude Childrens Research Hospital have cured babies with bubble boy disease through gene therapy involving a re-engineeredvirus, according to a newly published study.

St. Jude performed the therapy oninfants newly diagnosed withX-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 diseaseprevents 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.

Corresponding authors Dr. Ewelina Mamcarz and Dr. Stephen Gottschalk from St. Jude Children's Research Hospital. St. Jude performed a new therapy oninfants newly diagnosed withX-linked severe combined immunodeficiency (SCID-X1), a genetic condition called "bubble boy" disease, according to a study published in the New England Journal of Medicine's April 18 issue.(Photo: Peter Barta / St. Jude Childrens Research Hospital)

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

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

Brian Sorrentino(Photo: Courtesy of Memorial Park Funeral Home)

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.

Were 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.

Newborns with bubble boy disease, caused by a mutation inside a specific gene,must be placed inprotective 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."

David Vetter had to stay inside a bubble in Houston on Dec. 17, 1976. Vetter was born with a genetic disorder leaving him no natural immunity against disease. Vetter died in 1984.(Photo: AP)

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 Mamcarzof the St. Jude Department of Bone Marrow Transplantation and Cellular Therapy. We dont 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.

The gene therapy works like this: A deactivated virus is inserted into the patients bone marrow, which deliversthe 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.

Dr. Ewelina Mamcarz, first and corresponding author of a study published in the New England Journal of Medicine about a therapy performed at St. Jude Children's Research Hospital oninfants newly diagnosed withX-linked severe combined immunodeficiency (SCID-X1), a genetic condition called "bubble boy" disease.(Photo: Peter Barta / St. Jude Childrens Research Hospital)

It takes about 10 days from the time the cells are taken outto 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 wasnt 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.

Gael Jesus Pino Alva, 2, and his mother, Giannina Alva. Gael was treated with a new therapy designed to fight X-linked severe combined immunodeficiency (SCID-X1), a genetic condition known as "bubble boy" disease, at St. Jude Children's Research Hospital.(Photo: Peter Barta / St. Jude Childrens Research Hospital)

Current treatments for bubble boydisease are limited. Bone marrow transplants from compatible sibling donors are the best bet, but most patientslack a properdonor.

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 clinicaltrial 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 treatother 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.

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Downingsaid the search for a cure has been a journey spanning more than a decade. Early gene therapy studies with the viral vectorsled 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, Downingsaid.

The patients' quality of life following the treatmentshows theyindeed 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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