Gene therapy successfully treats 'bubble boy' disease

Infants born with a severe immunodeficiency disorder have been successfully treated in a new gene therapy trial. 

Seven of the eight children in the trial with X-linked severe combined immunodeficiency (SCID-X1) – often dubbed 'bubble boy' disease – now have a full immune system.

'These patients are toddlers now, who are responding to vaccinations and have immune systems to make all immune cells they need for protection from infections as they explore the world and live normal lives,' said first author of the study Dr Ewelina Mamcarz at the St Jude Children's Research Hospital in Memphis, Tennessee.

'This is a first for patients with SCID-X1,' she added. The results were published in The New England Journal of Medicine.

The children were born with a mutation in the gene, Il2RG, necessary for correct immune system development. The gene therapy used an engineered virus to replace the faulty gene with a functional copy. 

The seven children are now producing functional cells that constitute a full immune system, including T cells, natural killer cells, and B cells.

SCID-X1 and similar disorders are often called 'bubble-boy' diseases, owing to the plastic enclosures that were commonly used to protect children with the disorder from possible infections. Because they lack a proper immune system, contact with the outside world poses a major infection risk, and even a common cold can be fatal. The disease predominantly affects boys.

Until now, the best treatment had been a bone-marrow transplant from a donor-matched sibling. However, this option is available to less than 20 percent of patients. 

Consequently, efforts have focused on trying to deliver a functional copy of the gene to children who are unable to receive a transplant. 

Approaches to engineer a suitable virus that was capable of replacing the mutated gene had mixed results: prior studies reported improved immune response but caused leukaemia in some patients (see BioNews 439). 

In this latest trial, researchers used a non-infectious, disabled relative of the HIV virus to replace the faulty gene in the cells that make up the immune system. In addition, they treated patients with a low dose of chemotherapy prior to treatment, in order to optimise growth of the new, functional stem cells in the bone marrow. 

The children involved in the study have no signs of leukaemia up to two years after their treatment. 

While continual monitoring of the children is required to verify the long-term outcome, the results from the trial are a first, and the researchers hope a similar approach could be used to treat other disorders such as sickle cell disease. 

'From a physiological point of view and from a quality-of-life point of view, this is a cure,' Dr James Downing, president of St. Jude Children's Research Hospital told Nature News. 'Will it be a durable cure? Only time will tell.'