Born with “bubble boy” disease, 4-year-old has normal life after gene therapy

20150108_CaceresFollowUp-9Seated in an exam room on the sixth floor of Boston Children’s Hospital, Sung-Yun Pai, MD, speaks mother-to-mother—not doctor to patient’s mother—with Marcela Caceres, who has just asked whether she should take extra precautions if her 4-year-old son Agustin is exposed to chickenpox. The answer is no. “I’m a mother too, and a good mother also knows when to back off,” Pai tells her. “It’s important for him to have a normal life.”

“It’s hard for me to really accept that that’s the case,” Caceres says, “but I’m working on it.”

If Caceres has trouble shedding her instinct to over-protect, it’s for good reason. Agustin was born with X-linked severe combined immune deficiency (SCID-X1)—“bubble boy” disease—and it can be difficult for Caceres to believe that the gene therapy Agustin had four years ago has cured him of the illness that killed her first-born child, Ivan, in 1999 at the age of 5 months. The Caceres family has come to Dana-Farber/Boston Children’s Cancer and Blood Disorders Center from their home in Buenos Aires for Agustin’s annual post-treatment checkup, which is conducted with the aid of an interpreter.

Boys with SCID-X1 have no functioning immune system because their bodies fail to produce T-cells, the white blood cells that are critical for fighting disease and infection. Marcela and Alberto Caceres’s second child, 8-year-old Jeremias, was tested at birth and did not have the disease, but Agustin, also tested at birth, did. For three months, he lived at home in isolation to protect him from infection. His parents wore sterile hospital garb—gown, gloves and mask—whenever they interacted with him, and they kept the two brothers apart lest Jeremias be carrying a cold or other illness that could be life-threatening to Agustin. Left untreated, boys with SCID-X1 usually die before their first birthday.

Jeremias proved not to be a match for a stem cell transplant, the conventional treatment, and, likewise, a search of bone marrow registries did not identify a fully matched unrelated donor. In October 2010, the family traveled to Boston so Agustin could participate in a new gene therapy trial for SCID-X1 that uses a specially created viral “vector” to deliver the corrective gene through a transfusion.

Sung-Yun Pai, MD, and Agustin share a smile.

The trial is designed to address the serious problems that surfaced in earlier European trials when one-quarter of patients developed treatment-related leukemia. According to a recent article in the New England Journal of Medicine, early results—which include Agustin’s progress—indicate that the redesigned vector is as effective as the original one and also appears to be safer. It does not turn on the cancer-promoting genes that the earlier vector sometimes activated. As required by the federal Food and Drug Administration, researchers will follow Agustin and other children on the clinical trial for 15 years.

At Agustin’s four-year checkup, Pai tells the child’s parents that his T-cell count is normal. She and Agustin’s parents discuss plans to try to wean the child from the monthly intravenous infusions of immunoglobulins to boost his resistance to infection. Mostly, however, the visit seems more like a typical pediatric checkup than followup for a rare, life-threatening illness as Pai assures Agustin’s parents that their questions about his occasional cough and tendency to tiptoe are ordinary concerns.

“My plan,” Pai tells them, “is when he gets married, I need to be invited.”

“We are always going to be in touch with you,” Marcela Caceres replies.  “This is also your son.”