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. Last Updated: 07/27/2016

Gene Therapy Successfully Treats Bubble Boys




For the first time, scientists have successfully used gene therapy, the replacement of defective genes with working copies, to save the lives of several infants who might otherwise have died of a severe immune disorder.


Researchers said the achievement, announced Thursday, was the first unequivocal success for gene therapy, a field whose widely heralded promise has until now ended in disappointing results.


The work involved three babies who could not grow complete immune systems. The only other treatment for the condition, a form of severe combined immune deficiency, is a bone marrow transplant, which works just 60 percent of the time. Otherwise, patients must live in germ-free bubbles or fall prey to the ever-present microorganisms that normal people easily fend off.


In a report of the work in Friday's issue of the journal Science, Dr. Alain Fischer, a professor of pediatric immunology at the Hospital Necker-Enfants Malades in Paris and his colleagues describe the course of two of the babies, ages 11 months and 8 months at the time of treatment.


Three months after their gene therapy, the researchers recounted, the babies were home from the hospital, living like any other children. Ten months later, their immune systems were normal. Ordinarily, infants born with SCID (pronounced like skid), die before their first birthdays unless they remain in a germ-free environments.


In a footnote, the researchers said they had successfully treated a third baby, who was 1-month-old at the time. In a telephone interview, Fischer said he had since treated two more babies and was waiting to learn whether the effort succeeded with them as well.


"We are very happy and the families are very happy," Fischer said. "It is a success today. Then the next question is, 'How long will it be a success?' It may be that after some time there will be a decline in these cells and that sooner or later we will have to treat them again. We hope that if this happens it will not be for a very long time."


Gene therapy experts were exuberant. "It's a very exciting study," said Dr. R. Michael Blaese, who was a member of a medical team at the National Institutes of Health that attempted the first gene therapy on a human patient nearly 10 years ago.


Blaese, now the head of the human therapeutics division at ValiGen, added: "This would probably be the first example in any disease where gene therapy could be a fully successful treatment. You can't distinguish these patients from normal."


The success comes after a decade in which, according to the National Institutes of Health, more than 390 gene therapy studies were initiated, involving more than 4,000 patients and more than a dozen medical conditions. While those doing the research expressed confidence in its promise, critics said many of the companies formed to capitalize on the technology exaggerated preliminary data in hopes of raising capital.


And, at times, some scientists promised more than the technology was ready to deliver, leaving the field a target for accusations that patients were being endangered by reckless experiments that were doomed to failure.


"We've all been so burned by saying, 'Ah, this looks like it worked, that looks like it worked,'" said Dr. W. French Anderson of the Keck School of Medicine at the University of Southern California, and a member of the team that attempted the first gene therapy in 1990. "Now when it finally looks like something is working, I don't want to be in the position of saying the same words. We've all been criticized for hyping too much."


The babies treated by Fischer had a rare disorder known as severe combined immunodeficiency-X1, or SCID-X1, which almost exclusively affects boys, occurring once in every 75,000 live male births. It is caused by mutations that destroy the function of a gene that is needed to make T cells, a class of white blood cells.


In a sense, the condition is a perfect target for gene therapy. With SCID-X1, the cells that need a new gene are readily accessible in the bone marrow, which is relatively easy to remove.


Even better, if functioning genes actually get into the marrow cells of patients with SCID-X1, those genetically corrected cells will proliferate and displace cells with the defective gene. That is because, as the body tries to grow a complete immune system, it sends waves of chemical signals to the bone marrow to stimulate it into providing T cells. T cells with the defective gene start to grow and then die. Any cells with a functioning gene will be fueled by the body's hormones and will grow rapidly to populate the bone marrow.


Fischer said he began working on gene therapy for SCID-X1 in 1993, as soon as the missing gene was identified. He studied the treatment in mice and in the laboratory, attempting to insert the gene into patients' cells for six years before trying to treat patients. Last year, he said, he decided "there was a serious chance that the treatment could work in this particular disease," and the success with the first babies was the result.