Gene therapy beneficial but not permanent in serious immune disorder

Early trials in patients with chronic granulomatous disorder (x-CGD), a recessive X-linked condition that affects the immune system, have shown signs of success following the use of gene therapy. The observed boost in immunity of those undergoing treatment was only temporary, however, and the faulty gene causing x-CGD was not corrected permanently.

Five patients with x-CGD were treated by doctors at Great Ormond street Hospital (GOSH), London and UCL's Institute of Child Health. 'Gene therapy continues to make exciting progress. This is the third immune disease to respond to gene therapy in our programme', said Professor Adrian Thrasher, a senior member of the team. The response of the most recent patient treated with a new vector was 'very good', he said.

X-CGD is a rare inherited disorder that affects four in one million people. People affected by x-CGD have a faulty bone marrow gene which means the immune cells that fight off fungal and bacterial infections do not function correctly. This leaves patients exposed to infections, which can be potentially life-threatening and can lead to long periods in hospital.

The only cure for x-CGD is through bone marrow transplantation. Some patients are not able to undergo the procedure, however, and finding a matching donor can be difficult. For these patients, gene therapy may be the only option.

Using an inactive virus to act as a vector, the researchers inserted a working copy of the faulty gene into the patients' blood stem cells. The stem cells were then reintroduced into the body where they can produce the immune cells deficient in patients with x-CGD.

X-CGD is the third immune disease to have been treated with a positive outcome at GOSH following reported successes in treating X-linked severe combined immunodeficiency (x-SCID) and adenosine deaminase severe combined immune deficiency (ada-SCID).

Some of the patients involved in the trials for x-SCID and ada-SCID showed a permanent correction in their immune system. However, two patients, one based at GOSH and the other who took part in a trial at a sister facility in France, developed leukaemia. The researchers say they have developed new vectors in an attempt to reduce this risk.

Since most immune diseases have a similar underlying cause, Professor Adrian Thrasher is hoping that the success in the x-CGD trial may be indicate future breakthroughs for other immune disorders are not far away.

'We currently hope to treat patients with four different immune diseases at GOSH this year. We reported in August 2011 that […] patients with the first two diseases on our programme, x-SCID or ada-SCID showed clear clinical benefit. Trials for a fourth disease, Wiskott-Aldrich syndrome, have also recently started, while those for cancer, HIV (human immunodeficiency virus), and inherited skin disorders are close to clinical application', said Professor Thrasher.

Meanwhile, the new vector trial may provide hope to others affected by x-CGD. 'The CGD Society started funding gene therapy projects in 1994 and we are hugely excited by these developments', said Susan Walsh, head of research and specialist services at the charity, the CGD Research Trust. 'In 2005 we took a major strategic decision to allocate over £1m into developing a new and safer vector. It's wonderful to see this work come to fruition and know that gene therapy is being used to help very seriously ill patients with CGD'.