Children Treated with Gene Therapy for Adenosine Deaminase Deficiency Still Doing Well a Decade Later

How are the ten children who participated in a gene therapy clinical trial doing more than a decade later? The physicians behind the trial of these young patients with severe genetic immunodeficiency just provided an update on their health condition.

Genes

Gene therapy to treat Adenosine Deaminase deficiency

In 2009 and 2012, ten children participated in a phase 2 clinical trial to treat their incurable genetic disease, ADA (Adenosine deaminase deficiency)-SCID (severe combined immunodeficiency). The young patients had a severe deficiency of adenosine deaminase, an enzyme essential for immune system development, resulting in severe immunosuppression. Without treatment, most of the children affected by this condition would die before the age of two years from opportunistic infections that their immunity has failed to eradicate.

The ten patients, ranging in age from 3 months to 15 years, were treated with gene therapy. Their own bone marrow stem cells were modified with a gene therapy vector in the laboratory. The vector, derived from a mouse gammaretrovirus, carries the adenosine deaminase (ADA) gene to restore its activity by integrating it into the genome of the harvested cells. As in an autologous transplant, the modified cells were injected back into the children. After almost ten years of treatment, doctors from UCLA reported on the state of the treated subjects in the journal Blood.

90% of the children improved

Almost all of the children are healthy now and have not relapsed. For nine of them, the treatment was successful. However, it did not work in the case of a patient, who was 15 years old at the time. “We already saw in the early years that this treatment worked, and now we can say that it not only works but that it does so after more than 10 years,” explains Daniel B. Kohn, professor at the University of California and leader of this research.

During these ten years, the immune system of the nine children has developed properly and robustly, and they have not needed a gene therapy “booster” or a bone marrow transplant from a donor. Some of the treated subjects even have 100 times more ADA-expressing blood stem cells than the other participants. Now doctors want to achieve the same results in all ADA-SCID patients.

The integration of the gene therapy vector into the genome can have serious consequences, such as the development of cancer. Doctors have closely followed the expression of the cell reproduction genes in the modified cells. In some children, they are overexpressed, but so far no cancer has developed. This is also a point on which researchers are constantly improving. “The knowledge that gene therapy can have a long-term effect on ADA-SCID for more than a decade is important for the development of new gene therapies for this and other diseases,” he concludes.