Gene therapy treats children with rare immune genetic disorder

Gene replacement therapy was used to restore immune system function in children born with a rare immunodeficiency disorder called ART-SCID, researchers report.

A new therapy for ART-SCID (Artemis-deficient severe combined immunodeficiency), pioneered at the University of California, San Francisco, aims to restore the function of a defective gene at the root of the condition. It involves replacing the gene that codes for the protein Artemis, which is dysfunctional in ART-SCID patients. Results of the first clinical trial show either partially or fully restored immune systems in all ten infants who took part.

'The course of their disease is already much better than with usual treatment,' said Professor Morton Cowan, paediatric immunologist and the trial's principal investigator. Professor Cowan has previously treated more than 30 children with ART-SCID by standard bone marrow transplants. 'I have never seen results like this in any of the other children. It's amazing.'

Around 40-100 babies in the USA are born with SCID every year. Children with SCID lack a functioning immune system, with most children dying from an infection before the age of two, unless treated with a bone marrow transplant.

ART-SCID is a rare subtype of the condition caused by a defect in the gene that codes for the protein Artemis. Without Artemis, the bone marrow cannot produce T cells and B cells, which are important immune cells.

The gene replacement therapy involves extracting stem cells from a patient's bone marrow and introducing the gene to produce functional Artemis. The gene addition is performed using a modified virus, taking advantage of the natural properties of lentiviruses to insert DNA into the genome in a semirandom manner. The modified cells are then quality controlled and infused back into the patient intravenously.

Similar gene replacement approaches have been used previously in patients with other genetic forms of SCID (see BioNews 1118, 1095 and 996). However, its use in ART-SCID is promising as these patients tend to respond worse to standard bone marrow transplants.

After receiving therapy, follow-up blood tests showed that all children produced T cells and B cells, and five had fully functioning immune systems. With time, all participants should develop fully functional immune systems and be able to lead normal lives, said Dr Jennifer Puck, paediatric immunologist and co-leader of the study.

'For patients in the trial to achieve full T-cell immunity is remarkable. B-cell recovery takes longer, but so far it appears that patients also have a much better chance of B-cell reconstitution than with a normal bone marrow transplant,' Dr Puck continued.

At this stage, the researchers are reluctant to claim they have cured the disease. They plan to follow the children for longer to observe how the response develops over time.

'The study may have also missed other potential side effects because of its small sample size,' Professor Vincent Bonagura from the Feinstein Institutes for Medical Research, New York who was not involved in the trial said 'But ultimately the treatment is a significant advancement in treating Artemis-deficient SCID.'