Gene therapy success

Ten years ago, children with a severe and fatal form of immune disorder at Great Ormond Street Hospital (GOSH), were given the chance of a cure involving a highly experimental and revolutionary new treatment – gene therapy. Now researchers at GOSH have announced the results of decades’ worth of painstaking work to ensure the safety of this ground-breaking technique.

Children with immune disorders are compromised in their ability to fight off infection. Severe combined immunodeficiency (SCID) – a previously lethal condition – means children are born with almost no functioning immune system of their own.

Because of a defect in one of a number of genes crucial to the body’s production of immune cells, children with SCID are unable to mount an attack against disease, meaning any infection they are exposed to can prove fatal.

These children therefore have to be completely isolated from their surroundings in a sterile environment, giving rise to the common name for the condition – ‘boy in a bubble’ syndrome.

“These children were some of the sickest we’d ever seen,” says Bobby Gaspar, Professor of Paediatric Immunology at the UCL Institute of Child Health, and one of the team who has helped to deliver Great Ormond Street Hospital’s pioneering gene therapy programme.

“We knew that our best treatment at the time – a bone marrow transplant – was simply not going to work in a significant number of these cases, especially those children for whom we couldn’t find a matched bone marrow donor.”

The solution lay in a technique which, until ten years ago, had never been tested in a paediatric setting. It relied on removing a sample of the patient’s bone marrow – the building block of all of the body’s immune cells – and exposing them to viruses carefully modified to carry a functioning copy of the faulty gene which causes SCID.

This modified virus is then incubated with the bone marrow, where it transfers and integrates the functioning copy of the gene into the DNA of the recipient cells.

Now armed with the vital genetic instructions which they previously missed, the bone marrow cells are re-introduced back into the patient, where they grow to produce the full spectrum of immune cells crucial for fighting disease.

GOSH runs more gene therapy trials for immune deficiency in children than any other centre in the world.

With ongoing support, the research team hopes to roll out the hospital’s gene therapy programme to a number of other diseases, allowing many more patients to be offered this ground-breaking new therapy as a front line approach.