Bursting the SCID-X1 bubble

The Caceres family

Agustin Caceres’s baptism was the only time his family was allowed close to him. But even then, anyone who came in contact needed to wear masks, gloves and gowns. After the ceremony, Agustin went back into isolation, along with his mother Marcela, who stays with him and only comes out for meals.

Agustin spent much of his life separated from the world because he has a form of X-linked Severe Com­bined Immunodeficiency—or SCID-X1—better known as “bubble boy disease.” It affects only boys, leaving their bone marrow unable to make T-lymphocytes, the white blood cells that fight germs and infection.

To keep Agustin safe, his father, Alberto, and his four-year-old brother, Jeremias, live in a separate bedroom. At one point Jeremias even left his nursery school to make sure he couldn’t bring home any infections his baby brother might catch.

Unfortunately, this is not the Caceres’s first experience with SCID-X1; their first son was also born with the disease and died from it before he was even 5 months old. So when Jeremias was born healthy, the family banked stem cells from his umbilical cord blood to benefit future treatment, should they have another son born with the disease. At first doctors were hopeful Jeremia’s stem cells could be used to treat Agustin, but the boys’ tissues weren’t compatible. Without interven­tion, Agustin was likely to die from a bacterial or viral infection before his first birthday.

Now that Agustin’s T-cell is on the rise, his father can actually hold him

In their search for a donor, Dr. Matías Oleastro, Agustin’s immunologist, learned that Children’s Hospital Boston was recruit­ing for a clinical trial that was attempt­ing to use gene therapy to cure SCID-X1. Wasting no time, Oleastro sent the trial’s principal investigators, Luigi Notarangelo, MD, and Sung-Yun Pai, MD, a sample of Agustin’s blood. Based on what they saw, Notarangelo and Pai selected Agustin as a participant in the international trial.

“The main advantage of gene therapy is that patients would receive their own cells, so there is no chance of graft-versus-host disease,” explains Pai, of Children’s Division of Hematology/Oncol­ogy. “There’s also no time delay in finding a donor and no need for chemotherapy.”

In December, Agustin underwent the gene therapy procedure. His bone marrow was extracted and purified and blood stem cells manipulated in Dana Farber’s Cell Manipulation Core Facility (CMCF) were used to carry the new replacement gene. The gene was delivered by a specially engineered virus, called a vector, which infects specific cells without spreading to other cells. A few days later, the treated cells were reinfused back into Agustin.

The hope was that the treated cells would turn on the new gene, enabling them to make T-cells. Agustin’s T-cell count was only 5 when he arrived at Children’s, far too few to protect him. Over time, his doctors hoped, there would be enough healthy blood stem cells to make Agustin an ample supply of T-cells.

By early May Agustin, now 10 months old, is chubby and full of smiles, sticking out his tongue and blowing bubbles as his parents cuddle him.  “He has gained weight, and all of his organs are functioning normally,” says Notarangelo. “His muscle tone and behavior are appropriate for his age. Basically he’s a healthy child.”

Agustin’s T-lymphocyte count is now up to about 170. While it’s not yet up to normal levels, he’s producing more and more T-lymphocytes as time goes on, which has doctor optimistic about his future. “It’s a steady and impressive increase, like a rocket,” says Notarangelo. “It shouldn’t take too long before he reaches a normal count.”