© 1998 by Oxford University Press
But upon arriving at Childrens Hospital Los Angeles, where two of the three infants were undergoing the procedure for a rare, inherited immune disorder known as ADA, Blaese had to wade through a sea of cars and TV cameras. There was no more excitement -- he later said -- than on the day actor Clint Eastwood was elected mayor of Carmel.
Some 5 years after their initial therapy, Blaese has somehow managed to protect the privacy of the infants and their families far better. But the infants' clinical course is public, and a partial follow-up of their medical status appears in July's Nature Medicine. All three children, one of whom was treated at the National Institutes of Health, are doing fairly well, he says, but the system -- inserting the ADA gene into stem cells harvested from the infants' cord blood -- is far from perfected.
One baby did come off enzyme replacement therapy, pegADA for 2 months, but was quickly put back on the drug when there was a suggestion that his clinical condition might be worsening because of weight loss and possible thrush, according to Blaese. His immunologic profile was mixed as well. While off the enzyme, the baby's T-cell counts stayed level and remained functional, but an anti-tetanus subset of these cells lost their ability to respond until the child was placed back on the drug, said Blaese.
What was more surprising, however, is what happened to natural killer cells and antibody-producing B cells, which disappeared rapidly in the infant when pegADA was stopped. This suggests, says Blaese, that even though the ADA gene was transduced successfully into the T cells, the granulocytes, and the monocytes, that did not happen for the other immune system cells.
"We still don't know exactly what's happening," he admits. "But we believe and these experiments clearly show that the T cells are the cells that need to get the [ADA] gene for sure and they do have a selective advantage," which means that genetically corrected T cells survive longer than those without the correction.
By itself, though, that does not appear to be enough to alter the course of ADA, which without any treatment results in death in the first years of life. That finding is "not terribly surprising for a first go-round," says Blaese, who thinks future attempts to alter stem cells genetically hold greater promise because of a new, more active vector and cytokines that may better preserve the function of B cells.
-- Susan Jenks
Gene Therapy Infants Faring Well
As the principal investigator of a stem cell study in infants, R. Michael Blaese, M.D., had tried to keep a lid on the public attention surrounding the novel gene therapy.
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