Gene therapy shows clinical effect in third immune disease.
Doctors at Great Ormond Street Hospital/UCL Institute of Child Health report that five patients with x-CGD have responded to gene therapy, showing clear clinical benefit. Patients saw a clear but temporary improvement in their immune system, which helped with their serious illness at the time. However the correction of the gene defect was not permanent.
This is the third immune disease which has responded to gene therapy at GOSH and demonstrates the continued potential of research into this treatment technology.The work has been funded by National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital, AFM, GOSHCC, The Chronic Granulomatous Disorder Society, Wellcome Trust, and the MRC.
x-CGD is an inherited, life threatening immune disease where children have normal protection from viruses but cannot produce working phagocytes (white blood cells), and so have reduced protection from fungi and bacteria. As a result the patients can suffer from severe infections, require constant medication, and suffer social restrictions to reduce the risk of disease.
Great Ormond Street Hospital for Children and the UCL Institute of Child Health have treated 4 CGD patients over the years (reported in Molecular Therapy.) A fifth patient has been treated with a new vector and is also doing well. The patients did not show a permanent correction of their gene defect but they have recovered from their illness as a result of transient correction of their defect, so we have demonstrated therapeutic effect. 
In this gene therapy, a virus acts as a vector, to put a working copy of the gene concerned into a sample of the patient’s blood stem cells. These modified blood stem cells are reintroduced to the body and then produce the necessary working cells for the immune system. We have developed a new vector, that we hope will be both safer  and more efficient .
A multicentre European clinical trial for the new vector is being developed in collaboration with Genethon in France. In the meantime we have treated one patient with the new vector as he was very sick. He had very good recovery of activity, which shows that the new vector works very well. The focus of the new clinical trial is to gain more permanent correction of the gene defect and establish long term followup data.
Professor Adrian Thrasher said “Gene therapy continues to make exciting progress. This is the third immune disease to respond to gene therapy in our programme, and the response of this patient to our new vector was very good. We currently hope to treat patients with four different immune diseases at GOSH this year.  We reported in August 2011 that 14/16 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, and inherited skin disorders are close to clinical application.”
Dr. Susan Walsh, Head of Research and Specialist Services for the CGD Society, said “The CGD Society started funding gene therapy projects in 1994 and we are hugely excited by these developments. 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”.
 GOSH has reported success in x-SCID and ada-SCID. In both these diseases, all patients showed clinical benefit and some had permanent correction of their immune system, amounting to a cure.
 As was widely reported, some patients on the French trial and one on the GOSH trial developed leukaemia. The GOSH patient with leukaemia is in remission. It has been possible to develop new vectors that we intend to reduce this risk.
 The vector is a virus which delivers a working copy of the gene into the patient’s own stem cells. These then grow, so the patient should develop the full range of immune system cells. Improving the efficiency of gene transfer is important to deliver more effect.
 x-SCID, ada-SCID, x-CGD, Wiscott-Aldrich Syndrome
The National Institute for Health Research provides the framework through which the research staff and research infrastructure of the NHS in England is positioned, maintained and managed as a national research facility. The NIHR provides the NHS with the support and infrastructure it needs to conduct firstclass research funded by the Government and its partners alongside high-quality patient care, education and training. Its aim is to support outstanding individuals (both leaders and collaborators), working in worldclass facilities (both NHS and university), conducting leading-edge research focused on the needs of patients. www.nihr.ac.uk
The Chronic Granulomatous Disorder Society (CGD Society) is a national charity representing and supporting the interests and welfare of all children and adults born with CGD. The CGD Society provides patient support and advocacy services for families affected by CGD as well as investing in scientific and clinical research to help develop more effective treatments and cures for CGD. www.cgdsociety.org