MEMPHIS — A new type of gene therapy pioneered at St. Jude Children's Research Hospital appears to build fully functional immune systems in babies born with the so-called "Bubble Boy" disease, offering hope of a permanent cure for kids who otherwise might die before their second birthdays.
St. Jude researchers recently reported that four months after they were treated, most of the patients enrolled in a clinical trial had immune systems for the first time. Many were making their own antibodies and no longer required isolation to protect them from infections and pathogens.
"What we're finding is the gene therapy is working very well. The patients ... are having their immune systems restored," said Dr. Brian Sorrentino, a member of St. Jude's department of hematology, who led the study along with hospital colleague Dr. Ewelina Mamcarz.
The patients, aged 2 months to 13 months, were born with X-linked severe combined immunodeficiency disease, which renders their bodies unable to produce T-cells, B-cells and natural killer cells — the pillars of the immune system. The disorder stems from a mutation of a protein-coding gene that almost exclusively affects males and occurs at a frequency of 1 in every 50,000 to 100,000 live births.
Although St. Jude is best known for fighting pediatric cancer, the immunodeficiency disorder is among the catastrophic childhood diseases that the hospital was founded to combat, Sorrentino said.
"These are some of the sickest children in the hospital. ... It's smack dab in the middle of our mission," he said.
The disorder gained widespread attention through the 1976 movie The Boy in the Plastic Bubble, inspired largely by the true story of a Texas child who had to live in a sterile chamber because of his ravaged immune system.
Without treatment, kids with the disease often die by age 2. The best current treatment is bone marrow transplantation with a fully matched sibling, but some 80% of patients, including those in the trial, have no sibling match, meaning they would get fewer benefits and face higher risks of complications from the transplants.
To solve those problems, St. Jude re-engineered a virus that ferries a normal copy of the gene to replace the defective one. Scientists included safety features, such as genetic insulators, to ensure that the vector virus, as it is called, doesn't inadvertently activate potential cancer-causing genes nearby.
During the treatment, the patient's bone marrow is removed, and blood-producing stem cells are allowed to incubate with the re-engineered virus carrying the normal gene. Before the stem cells are processed and pumped back into the patient, a chemotherapy drug is introduced to make space for them in the bone marrow.
This fix enabled the patients' bone marrow to begin cranking out the three types of immune cells.
Of seven patients in the trial, five had developed immune systems within a few months, while another patient, who joined the test late, already is showing signs of establishing immune protection. No serious, unexpected complications from the treatment have been reported.
The patients, who were treated at St. Jude and a children's hospital in San Francisco, will be monitored in the future to confirm the long-term benefits of the therapy, Sorrentino said.
The promising results have inspired hope nationwide. John G. Boyle, president and CEO of the Maryland-based Immune Deficiency Foundation, said in an email that his group is "optimistic that this recent clinical trial offers further evidence and hope that gene therapy may be a practical treatment option for patients with SCID in the future."
The early findings from the trial mean researchers are "very close" to a permanent cure for the disease, said Jonathan Hoggatt, assistant professor of medicine at Harvard Medical School.
"What we need to do now is track these patients for a long time," Hoggatt said.
Sorrentino said the benefits of the gene therapy can translate into effective treatments for other genetic ailments, as well. "We think it's a paradigm for treating other diseases," he said.
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