UCLA stem cell researchers have achieved a remarkable 100% cure rate for children born with adenosine deaminase-deficient severe combined immunodeficiency (ADA-deficient SCID), commonly known as Bubble Baby disease, using a groundbreaking gene therapy approach developed over three decades of research.
Dr. Donald Kohn, a stem cell researcher at UCLA's Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, led the team that successfully treated 18 children with the life-threatening condition across two multi-year clinical trials conducted since 2009. All patients were cured without any side effects.
"All of the children with SCID that I have treated in these stem cell clinical trials would have died in a year or less without this gene therapy," said Kohn, a professor of pediatrics and of microbiology, immunology and molecular genetics at UCLA. "Instead they are all thriving with fully functioning immune systems."
Revolutionary Treatment Approach
The innovative therapy addresses a critical gap in treatment options for children with ADA-deficient SCID, which affects approximately 15% of all SCID patients. The condition occurs in an estimated 1 in 200,000 to 1 million newborns worldwide and can be fatal within the first year of life if left untreated.
During the treatment process, researchers remove blood stem cells from patients' bone marrow and genetically modify them to correct the genetic defect that prevents production of adenosine deaminase (ADA), an enzyme critical for generating healthy white blood cells needed for immune function.
Using a virus delivery system developed in Kohn's laboratory in the 1990s, the team inserts the corrected gene into the blood-forming stem cells. These genetically modified cells are then transplanted back into the patient, where they produce T cells capable of fighting infection and establish a fully functioning immune system.
"It's their own cells so it's a perfect match," Kohn explained. "And when it works ... they grow a whole immune system, and can lead normal lives."
Addressing Current Treatment Limitations
The gene therapy represents a significant advancement over existing treatment options, which include lifelong twice-weekly ADA enzyme injections that are expensive and often fail to restore optimal immune function, or bone marrow transplants from siblings that carry risks of rejection and graft-versus-host disease.
"Other current options for treating ADA-deficient SCID are not always optimal or feasible for many children," Kohn noted. "We can now, for the first time, offer these children and their families a cure, and the chance to live a full, healthy life."
Patient Success Story
The therapy's impact is exemplified by the case of Evangelina Padilla-Vaccaro, who was born with the condition in 2012. Her mother, Alysia Padilla-Vaccaro of Corona, California, recognized something was wrong just weeks after birth, despite initially being told her concerns were due to new mother stress.
Following diagnosis at six weeks old, Evangelina had to be kept in strict isolation, with family members required to shower, wear masks and gowns before any contact. After undergoing Kohn's gene therapy treatment, which took approximately seven weeks from start to finish including chemotherapy, Evangelina developed a new immune system and can now live normally.
"To finally kiss your child on the lips, to hold her, it's impossible to describe what a gift that is," Padilla-Vaccaro said. "I gave birth to my daughter, but Dr. Kohn gave my baby life."
Clinical Trial Results and Future Applications
The 18 patients treated in the clinical trials ranged in age from 3 months to 4 years at the time of treatment. All developed fully functioning immune systems following the gene therapy, with T cell counts rising and the ability to fight off illness and infection growing stronger over time.
The research team is now seeking FDA approval for the gene therapy to make it available to all children with ADA-deficient SCID. Additionally, the success has laid groundwork for extending the approach to treat sickle cell disease, with clinical trials planned 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," 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."
The research was supported by grants from the FDA, California Institute for Regenerative Medicine, and the National Institutes of Health, with additional funding from UCLA and its affiliated centers.
