Ten newborns with the rare genetic disorder known as bubble girl disease were cured with gene therapy, scientists revealed Wednesday. The treatment seems to have completely removed their immune defense babies without side effects or complications – a result researchers have been searching for decades through careful research and heartbreaking setbacks.
An earlier attempt to use gene therapy for the treatment of severe combined immunodeficiency disease, or SCID, was halted in 2003 after the researchers realized that the therapy gave the children cancer. Treatment revealed Wednesday does not seem to carry such scary side effects, and experts hope it can help promote cures for other rare genetic diseases such as sickle cell disease.
"It's a game switch," said Jennifer Hemall, a pediatric immunologist at the Children's Hospital in Philadelphia, who was not involved in the study. "For immunologists who follow this disease, gene therapy has always been out there as the hope of the future. It is exciting to see this wave of treatments actually become a reality."
Infants with SCID are essentially born without a functioning immune system. Without treatment, they rarely survive their first birthday and can be killed by infections as harmless as the cold. Such children were once isolated in sterile environments, giving rise to the term "bubble boy". Their unusual difficulties have received national attention and been characterized by films and TV shows.
The survival rate in recent years has increased with the advent of widespread screening testing and refinement of life-saving procedures such as bone marrow transplants. However, such treatments have had complications which often leave children dependent on regular immunoglobulin infusions or cause their new immune systems to attack their own body.
The new gene therapy – developed by St. Jude Children 's Hospital Hospital and UCSF Benioff Children' s Hospital in San Francisco and published in the New England Journal of Medicine – corrects the genetic deficiency of the baby 's DNA shortly after birth, causing their organs to generate missing parts of their immune system.
In interviews, the researchers said that they first took blood stem cells from the infant marrow. They used a modified virus as a means of delivering the correct copy of a defective gene to the stem cells of these patients. The corrected cells were then refilled into the patient, where they spread and created healthy immune cells.
To avoid causing carcinogenic genes as previous gene therapies, the researchers built "insulators" into the virus so that the neighbor's genes would not be affected when the virus did its insertion into the DNA. In another innovation, researchers gave their pediatric patients a small amount of chemotherapy to clear existing cells from the bone marrow before they reinfused the treated cells, giving the corrected cells a better chance of grasping.
The message was bittersweet for many on St. Jude Children's Research Hospital. Their team leader and senior author on paper, Brian Sorrentino, spent the last few months of his series on a deadly cancer to complete his experimental treatment.
Sorrentino was diagnosed at a young age with Hodgkin's lymphoma, said his widow, Suzanne Sorrentino. As modern treatments did not yet exist, his doctors treated him to the use of radiation which weakened his heart and produced lung cancer that killed him last November.
"Loss of hair, pain and pain in treatment, that's what made him determined to find new treatments for other diseases in children," his wife said in an interview.
Since the 1990s, Sorrentino had worked with other immunologists on gene therapy for SCID, but his work took on a new urgency in the last year and half of his life after his cancer diagnosis. Suzanne said. As he could no longer come to the hospital, St. Jude colleagues arranging conference calls and setting up business at Sorrentino's dining table. At that time, it was clear that the experimental procedure was successful. Several of their infant patients had grown into toddlers with perfectly normal immune systems.
"He told me he thought he was saved as a Hodgkin's child because there was something he thought he was going to do with his life," Suzanne said, her voice cracked as she recalled one of Her last conversation with her husband. "With the experiment working and the kids doing well, he felt it was a sign that he was achieving what he was supposed to. That it was time for him to go."
As newborn screening for SCID has become mandatory on Across the country, experts have found that the disease becomes more common than previously thought – occurs in as many as one in 50,000 infants.
There are several forms of SCID. Gene therapy for a variant called ADA-SCIDS is available in Europe. But a cure for the most common form – X-linked SCID, found only in boys – was amazing to now.
The disease exclaimed national attention in the 1970s with David Vetter. News Stores chronicled his life as he grew up cocooned in plastic. His story created the 1976 John Travolta movie "The Boy In the Plastic Bubble." And even after Vetter's death held something about the vulnerable insulating effects of the disease in the national consciousness and made a famous cameo in a Seinfeld episode and became the built-in performance of a Jake Gyllenhaal movie "Bubble Boy".
So far, the most effective therapy for SCID has transplanted blood-forming stem cells from a tissue-collected siblings donor, but most patients lack such donors. Half-matched and unrelated donors have also been shown to be life-saving, but often resulted in complications.
The first successful gene therapy study in 2000 by French doctors gave many researchers and patients hope that they could solve the molecular substrate of the disease instead of simply treating their symptoms. However, when leukemia was found in some of these patients, it temporarily stopped gentile testing in America and much of the world and sent missing researchers seeking answers.
"Leukemia stopped the field for a long time and rightly because people had to figure out what went wrong," said Jordan Orange, a pediatric immunologist at Columbia University who was not involved in St. The Jude study, however, helped develop a gene therapy for another immunodeficiency disease called Wiskott-Aldrich. "But that led us to the point now that we are finally starting to see actual cures on incurable conditions."