A small group of children that underwent gene therapy for a rare, inherited immune disorder are living normal lives years after the treatment, according to new research published in the New England Journal of Medicine (NEJM). The pioneering work was partly supported by the EU-funded CONSERT (Concerted safety and efficiency evaluation of retroviral transgenesis in gene therapy of inherited diseases) and CLINIGENE (European network for the advancement of clinical gene transfer and therapy) projects. Both projects are financed under the 'Life sciences, genomics and biotechnology for health' Thematic area of the Sixth Framework Programme (FP6).
The children had all been diagnosed with Severe Combined Immunodeficiency (SCID) caused by a lack of adenosine deaminase (ADA). ADA is an enzyme that is pivotal to the survival and functioning of our cells, and particularly to a type of white blood cell vital to the immune system known as a lymphocyte. Children with ADA-SCID have inherited a defective ADA gene from their parents, and so the children's bodies are unable to manufacture the enzyme.
Without ADA, the immune system cannot function properly, and affected children often die within a few months of birth as a result of infections like pneumonia, gastroenteritis and meningitis. The lack of ADA also wreaks havoc throughout the body, with sufferers often experiencing liver, skeletal and neurological problems, as well as slow growth and deafness.
Until now, the best treatment for children with ADA-SCID has been a bone-marrow transplant from a compatible sibling; however, this option is only open to a minority of patients. Bone-marrow transplants from other donors are possible, but carry a high risk of health problems. Affected children can also be treated with weekly injections of bovine ADA, but these have limited efficacy, and as the treatment must be continued throughout the patient's life, they are also extremely expensive.
In the study patients, doctors harvested the children's own blood stem cells from the bone marrow. In the lab, they used a virus to insert a healthy copy of the ADA gene into the cells. Meanwhile, the patients were given a small dose of a drug called Busulfan to make space in the bone marrow for the gene-treated stem cells. Finally, the patients' treated stem cells were returned to the bone marrow. There, they started to produce new blood cells containing the healthy version of the ADA gene.
In this latest study, the researchers evaluated the health of 10 children who had been treated with gene therapy 4 years previously, on average. They found that immune function and protection against severe infection had been restored in nine of these patients, allowing them to attend school, play with friends and generally experience a normal life. Crucially, the children appeared to have suffered no side-effects as a result of the gene therapy.
In contrast to other treatments for ADA-SCID, the researchers write, their protocol "offers excellent survival without serious complications, such as graft-versus-host disease. In addition, gene therapy is suitable for older children with SCID due to ADA deficiency, who have a higher risk of failure and complications after transplantation."
In addition to the 10 children studied in this latest research, 3 further patients have received the same treatment and are doing well. In 2005, the European Medicines Agency (EMEA) gave the protocol orphan-drug status.
The scientists hope that their findings will pave the way for the use of gene therapy in other inherited diseases such as immunodeficiencies and metabolic disorders.
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