Severe combined immunodeficiency treated successfully with gene therapy

By Dr. Ananya Mandal, MDAug 26 2011

Gene therapy can offer a cure for a rare condition that causes children’s immune systems to fail. In this rare condition, known as Severe Combined Immunodeficiency (SCID), inherited genetic mutations mean that babies are unable to fight off infection, severely limiting their chances of surviving more than a few years. Severe combined immunodeficiency (SCID) is a rare genetic disorder estimated to affect between 1 in 200,000 and 1 in 1,000,000 live births

In a new study researchers have shown the results of a trial that found that gene therapy was successful in 14 out of the 16 UK children they treated, allowing them to recover to lead normal lives. The technique works by introducing a working copy of the mutant gene, which provides the body with instructions on how to produce working immune system cells. The child followed for the longest time, nine years, still had functioning immune cells, showing that gene therapy works in the long-term.

Prior to gene therapy the only other option for children with the most common form of SCID was to receive a bone marrow transplant, which relied on finding a suitable match. This new technique, while not without risk, offers a credible treatment option in cases where a suitable donor cannot be found.

Doctors and researchers from the Institute of Child Health and Great Ormond Street hospital yesterday published research papers describing the long-term outcomes of gene therapy for children born with SCID. Their two papers, published in the journal Science Translational Medicine, describe positive long-term outcomes for the majority of the children they treated with gene therapy, who have been able to lead relatively normal lives since receiving treatment.

In the two longer-term follow-up studies recently published in Science Translational Medicine, the underlying genetic defect was repaired in four out of six patients with Adenosine Demaninase-Deficient SCID, and 10 out of 10 patients with X-linked SCID. Immune cell production was restored, and the effects persisted up to nine years after therapy (the most recent point of measurement). The procedure produced minimal side effects, and patients could attend typical schools.

Combining the results with the results of other studies shows that 30 patients with Adenosine Demaninase-Deficient SCID have been treated with gene therapy to date. All patients have survived (follow-up of 1-10 years) and 21 (67%) have been able to stop enzyme replacement therapy. The authors of the London study conclude that “these cumulative data with such a high level of safety and efficacy argue strongly that gene therapy should be considered as the first treatment option when no matched family donor is available”.

The results for trials for gene therapy for X-linked SCID performed in England, France and Italy have also shown it to be effective/effective within the course of trials.

The major danger is that gene therapy may activate an oncogene. These are genes (often a mutated form of a normal gene) that cause cancer. In the London trial, one of the 10 children treated for X-linked SCID developed leukemia. He was treated with chemotherapy and is now in remission. Leukemia also developed in four patients in the French trial. However, no cases of leukemia have been observed in any of the 30 patients treated with gene therapy for Adenosine Demaninase-Deficient SCID. It is unclear whether this occurrence is due to the nature of the DNA inserted to correct the mutation, the nature of the condition itself or some other factor.