Gene Therapy Cure for Children with “Bubble Baby” Disease

Gene Therapy Cure for Children with “Bubble Baby” Disease
(Image source)
Researchers have pioneered a stem cell gene therapy cure for children born with adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID), often called “Bubble Baby” disease, a life-threatening condition that if left untreated can be fatal within the first year of life. The breakthrough was developed over three decades of research to create a gene therapy that safely restores immune systems in children with ADA-deficient SCID using the patient’s own cells with no side effects. To date, 18 children with SCID have been cured of the disease after receiving the stem cell gene therapy in clinical trials at UCLA and the National Institutes of Health. (Source)

Children born with SCID, an inherited immunodeficiency, are generally diagnosed at about six months. They are extremely vulnerable to infectious diseases, and in a child with ADA-deficient SCID even the common cold can prove fatal. The disease causes cells to not create an enzyme called ADA, which is critical for production of the healthy white blood cells that drive a normal, fully-functioning immune system. About 15 percent of all SCID patients are ADA-deficient.

Currently, the only treatments for these children include injecting them twice a week with the necessary enzyme, a life-long process that is very expensive and often doesn’t return the immune system to optimal levels. These children also have the option to undergo bone marrow transplants from matched siblings, but matches are very rare or result in rejection of the transplanted cells which then turn against the child.

Since 2009 and over the course of a two multi-year clinical trials, researchers have tested two therapy regimens on 18 children with ADA-deficient SCID. During the trials, the patient’s blood stem cells were removed from their bone marrow and genetically modified to correct the defect. All of the 18 patients were cured.

The researchers used a virus delivery system that he first developed in the 1990s to insert the corrected gene that produces the missing enzyme necessary for a healthy immune system into the blood forming stem cells in the bone marrow. The genetically corrected blood forming stem cells then produce T cells that will fight infection. The researchers 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. 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.

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.

The video below give a scientific animation of the gene therapy cure of ADA-deficient SCID.