Chuck Bednar for redOrbit.com – Your Universe Online
A new stem cell gene therapy developed by researchers at UCLA is set to begin clinical trials early next year after the technique reportedly cured 18 children who were born without working immune systems due to a condition known as ADA-deficient Severe Combined Immunodeficiency (SCID) or “Bubble Baby” disease.
The treatment was developed by Dr. Donald Kohn, a member of the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, and his colleagues, and according to the university, it is able to identify and correct faulty genes by using the DNA of the youngsters born with this life-threatening condition.
Left untreated, ADA-deficient SCID is often fatal within the first year of a child’s life, reports Peter M. Bracke for UCLA. However, after more than three decades of research, Dr. Kohn’s team managed to develop a gene therapy that can safely restore the immune systems of children with the disease by using their own cells and with no noticeable 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, instead they are all thriving with fully functioning immune systems,” Dr. Kohn, who is also a professor of pediatrics and of microbiology, immunology and molecular genetics, said in a recent statement.
Children born with SCID have to be isolated in a controlled environment for their own safety, because without an immune system, they are extremely vulnerable to illnesses and infections that could be deadly. While there are other treatments for ADA-deficient SCID, Dr. Kohn noted that they are “not always optimal or feasible for many children.” The new technique, however, provides them with “a cure, and the chance to live a full healthy life.”
SCID is an inherited immunodeficiency that is typically diagnosed about six months after birth, the researchers said, and children with the condition are so vulnerable to infectious diseases that even the common cold could prove fatal to them. This particular form of the condition causes cells to not create ADA, an enzyme essential for the production of the white blood cells which are a vital component of a healthy, normally-functioning immune system.
Approximately 15 percent of all SCID patients are ADA-deficient, according to the university, and these youngsters are typically treated by being injected twice per week with the required enzyme. This is a process that must continue throughout a patient’s entire life, and even then it doesn’t always work to bring their immune systems to optimal levels. Alternately, they could undergo bone marrow transplants from matched siblings, but those matches are rare and the transplanted cells themselves are often rejected by the child’s body.
Dr. Kohn and his colleagues tested two therapy regimens on 18 ADA-deficient SCID over the course of two multi-year clinical trials starting in 2009. During the trials, the blood stem cells of the patients were removed from their bone marrow and genetically modified in order to correct the defect. All 18 of the patients were cured.
The technique used a virus delivery system first developed in Dr. Kohn’s laboratory in the 1990s – a technique which inserts the corrected gene that produces the ADA into the blood forming stem cells in the bone marrow. The genetically corrected blood-forming stem cells will then produce the T-cells required to combat infections.
“He and colleagues tested different viral vectors, modifying each and perfecting viral delivery as the best method to put the healthy ADA genes back into the bone marrow cells of the patients,” Bracke reported. “With the newly-transplanted cells now able to produce the needed enzyme, they use the powerful self-renewal potential of stem cells to repopulate the blood stream and the child develops their own new, fully-functioning immune system.
“The next step is to seek FDA approval for the gene therapy in the hopes that all children with ADA-deficient SCID will be able to benefit from the treatment,” the researchers added. “This cutting-edge research also lays the groundwork for the successful gene therapy to be clinically tested for treatment of sickle cell disease, with trials set to begin next year.”