(Front cover of CIRM’s 2016 Annual Report)
You don’t need data to see that Evangelina Vaccaro’s experimental stem cell therapy cured her of a devastating, often fatal immune disease. A quick look at her photos or videos shows a happy, healthy five‑year‑old with a full life ahead.
A look at the data
But the FDA doesn’t approve therapies based on one child’s outcome. Researchers must gather detailed, quantitative data from a series of clinical trials to prove a treatment is safe and effective. Each study also helps scientists refine procedures for the next trial.
A CIRM‑funded clinical trial published this week by a UCLA team in the Journal of Clinical Investigation did exactly that. Of the ten participants, nine—including Evangelina—were cured of adenosine deaminase–deficient severe combined immunodeficiency (ADA‑SCID), a disease that is usually fatal within the first year of life if untreated.
A long road for SCID
ADA‑SCID, also called bubble baby disease, is deadly because it destroys the body’s ability to fight infection. Children with the condition have a mutation in the adenosine deaminase gene, which causes early death of the cells that would normally form the immune system.
Without those cells, babies with ADA‑SCID are born without a functioning immune system. Even a common cold can be fatal, so they must live in extremely clean environments with limited contact with family and no outdoor play.
Different treatments
A few treatments exist, but each has limits. The primary option is a blood stem cell transplant from a matched sibling. Matches are rare, and imperfect matches can cause serious, life‑threatening complications. Another option, enzyme replacement therapy (ERT), requires twice‑weekly injections of the missing adenosine deaminase enzyme. It is expensive, and its ability to restore the immune system varies over time.
The current study, led by Don Kohn, avoids donor cells and enzyme therapy by repairing the patient’s own cells. Researchers collect blood stem cells from a bone marrow sample and insert a functional copy of the adenosine deaminase gene in the lab. Before the transplant, patients receive drugs—similar to cancer therapies—that clear out part of the faulty immune system to make room in the bone marrow. The repaired stem cells are then returned to the body, where they settle in the bone marrow and generate a healthy immune system.
The first ten
The ten patients were treated between 2009 and 2012 and monitored for at least four years. As of June 2016, nine patients—all infants except one eight‑year‑old—no longer need enzyme injections and now have functioning immune systems. They can play outside, attend school, and recover from everyday infections. The tenth patient, who was fifteen at the time of treatment, did not benefit, suggesting early intervention is crucial. No serious side effects were reported.
A clinical trial success
This isn’t the first stem cell gene therapy trial to successfully treat ADA‑SCID. Kohn’s team and others have run similar trials for decades, and this study builds on those earlier results. In a 2014 press release about the preliminary findings, Kohn explained why follow‑on trials are essential:
“We were very happy that over the course of several clinical trials, and after making refinements and improvements to the treatment protocol, we are now able to provide a cure for babies with this devastating disease using the child’s own cells.”
The team’s next step is securing FDA approval to offer this treatment to all children with ADA‑SCID. To move toward that goal, they are running another trial that tests a frozen version of the repaired blood stem cells. Freezing the product gives researchers more time for safety testing before transplanting the cells. It also makes the therapy easier to ship to children who live far from the gene‑therapy labs. In November of last year, CIRM’s Board awarded Kohn’s team $20 million to support this work.
If all goes well, this therapy will become the first stem cell gene treatment approved in the U.S. We look forward to adding many more photos beside Evangelina’s as more children are cured of ADA‑SCID.
Related posts
• UCLA team cures infants of often-fatal “bubble baby” disease
• Progress to a cure for bubble baby disease
• CIRM-funded therapy helps “bubble babies” lead a normal life
UAB hospital for children is testing my 2 1/2 grandson for this disease. Finally, after so many test they are finding out its a form of this. We will know for sure next week then maybe they can cure him.