Bursting the Bubble of Bubble Baby Disease

UCLA: Only weeks after giving birth to fraternal twins in 2012, Alysia Padilla-Vaccaro felt something was wrong with one of her daughters, Evangelina. “I was told that it was the stress, or the fear of being a new mom, but I just knew something wasn’t right,” says Padilla- Vaccaro. “Then I was informed that Evangelina had absolutely no immune system, that anything that could make her sick would kill her. It was literally the worst time of my life.” The baby had a genetic condition called adenosine deaminase-deficient severe combined immunodeficiency, or ADA-deficient SCID. Often called bubble baby disease — children born with SCID must be kept in controlled, isolated environments — the condition can, if untreated, be fatal within the first year of life.

Alysia and her husband Christian brought Evangelina from their home in Corona, California, to UCLA, where she underwent a new gene-therapy treatment developed by Donald Kohn, MD, professor of pediatrics and of microbiology, immunology and molecular genetics and researcher in the UCLA Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research. The treatment aims to restore the immune systems of children with ADA-deficient SCID using their own stem cells.
It worked. Evangelina’s new immune system developed without side effects. Her T-cell count began to rise, and her ability to fight off illness and infection grew stronger. Then Dr. Kohn told Alysia and Christian the good news: For the first time, they could hug and kiss their daughter and take Evangelina outside to meet the world. “To finally kiss your child on the lips, to hold her, it’s impossible to describe what a gift that is,” Padilla-Vaccaro says.
Evangelina is among 18 children with SCID who have to date been cured after receiving the therapy in clinical trials at UCLA and the National Institutes of Health. “All of the children with SCID whom I have treated in these stem-cell clinical trials would have died in a year or less without this gene therapy,” Dr. Kohn says. “Instead, they are all thriving with fully functioning immune systems.”
The cells of children with SCID do not create ADA, an enzyme that is critical for producing the healthy white blood cells needed for a normal, fully functioning immune system. About 15 percent of all SCID patients are ADA-deficient. Currently, there are only two treatment options for children with the disease. They can be injected twice a week with ADA — a lifelong process that is expensive and often doesn’t return the immune system to optimal levels. Or they can undergo bone-marrow transplants from siblings, but bone-marrow matches are rare and can result in the patient’s body rejecting the transplanted cells, which then turn against the child.

	Evangelina Padilla-Vaccaro’s medical team gathers around her on the day she received her gene-therapy stem-cell transplant.

To develop his therapy, Dr. Kohn and his team removed blood stem cells from the bone marrow of children with ADA-deficient SCID and genetically modified them to correct the defect. Using a virus-delivery system that he developed in the 1990s, Dr. Kohn inserted the corrected gene that produces the missing enzyme into the blood, forming stem cells in the bone marrow. The genetically corrected blood-forming stem cells then produced T-cells capable of fighting infection. With the newly transplanted cells now able to produce the needed enzyme, the research team harnessed the self-renewal potential of stem cells to repopulate the blood stream, and the children developed their own new, fully functioning immune systems.
The researchers’ next step is to seek U.S. Food and Drug Administration approval for the gene therapy, with the hope that all children with ADA-deficient SCID will be able to benefit from the treatment. Their research also lays the groundwork for the gene therapy to be tested for treatment of sickle cell disease; clinical trials are set to begin in 2015.
”We’ve been working for the last five years to take the success we’ve had with this stem-cell gene therapy for SCID to sickle cell,” Dr. Kohn said. “We now have the potential to take the gene that blocks sickling and get it into enough of a patient’s stem cells to block the disease.” For Padilla-Vaccaro and her husband, what matters most is now seeing both of their children thrive. “I gave birth to my daughter,” Padilla-Vaccaro says. “But Dr. Kohn gave my baby life.”