Enzyme Therapy Effective on Inherited Immune Deficiency : Hope Rises in Fight on Childhood Disease
In an advance that may lead to effective therapies for some inherited illnesses, researchers are reporting today early promise in treating a devastating childhood immune deficiency disease with injections of a manufactured form of the missing enzyme that causes the disease.
The first two patients treated with weekly intramuscular shots of the modified enzyme regained immune system function and are now free of serious infections, according to a report in the New England Journal of Medicine.
Both the children suffer from “ADA deficiency,” the rare disease that afflicted “David,” the boy who lived in a bubble in a Houston hospital for 12 years before he died in 1984.
One of them is Laura Cay Boren, the 4-year-old Kentucky girl who was featured in a Times article last April on the promise of gene therapy.
Life-Threatening Infections
Before the experimental therapy began last March, Laura Cay was frequently hospitalized with life-threatening infections. Now she has started to gain weight and is growing rapidly. Her medications, intravenous feedings and supplemental oxygen, have been greatly reduced, although she remains isolated from other children.
“This is a dramatic breakthrough in therapy for these patients,” said Dr. Rebecca Buckley of the Duke University Medical Center in Durham, N.C., one of the authors of the study. “We are very encouraged that Laura Cay should be able to go out in the real world in the near future.”
In addition to Laura Cay, the modified enzyme therapy has been given for about six months to a Nebraska girl, 10, who had received monthly transfusions of red blood cells since 4 months of age. The child, who had been hospitalized with pneumonia and a yeast infection of her throat before starting the treatment, has recovered fully and regained weight lost during her illness, according to the study.
In an accompanying editorial in the journal, Dr. Rochelle Hirschhorn of the New York University Medical Center called the discovery “a potentially exciting addition to our therapeutic armamentarium” that might be adapted for other genetic diseases.
Value Still to Be Proved
There were no side effects and no signs that the therapy became less effective during the 12 months it was tested. But Hirschhorn and Buckley cautioned that its long-term effectiveness remains to be proved.
Similar therapy may eventually be tried for patients with other genetic diseases in which toxic molecules accumulate in the blood stream because the enzyme that normally transforms these poisons into harmless substances is defective or lacking.
The potential therapy may also help prolong the lives of patients who are likely candidates for experimental gene therapy, in which a laboratory-engineered gene would be added to a patient’s own cells. Gene therapy is expected to be tried in the next several years.
ADA, or adenosine deaminase deficiency, is so rare that physicians know of fewer than 100 cases. But because this single-gene defect is better understood than other inherited illnesses, it has been the focus of a great deal of research, and children such as Laura Cay have been considered prime candidates for gene therapy.
Bone Marrow Transplants
Previously, physicians had unsuccessfully tried to cure Laura Cay with two transplants of her father’s bone marrow, an approach that works in some ADA patients.
They had also tried to replace the missing ADA enzyme with transfusions of red blood cells from normal donors, an approach that helps some children but usually does not provide sufficient amounts of the enzyme to restore the immune system.
Therapy with the modified polyethylene glycol-ADA enzyme has several advantages over previous unsuccessful attempts at enzyme replacement therapy for ADA deficiency, Buckley said. The modified enzyme can be given in large amounts. It also resists attack by other enzymes in the body that normally degrade the ADA enzyme. And it avoids problems caused by multiple blood transfusions, such as viral infections and high concentrations of iron in the body.
The key unanswered question is whether the modified enzyme will eventually be inactivated by antibodies produced as the patients’ own immune function improves. So far, this has not happened.
