The Trust supports inter-related collaborative work based in London, Frankfurt, Zurich and the USA.
New funding for 2009
IMPROVING GENE THERAPY FOR CGD: VECTOR DEVELOPMENT, TESTING AND CLINICAL APPLICATION
Dr Adrian Thrasher, Institute of Child Health, London. £192,782 over two years. Started September 2009.
Dr Manuel Grez, Institute for Biomedical Research, Georg-Speyer-Haus, Frankfurt, Germany. £217,703 over two years. Started January 2009.
Gene therapy is being considered as a potential curative treatment of several immunodeficiencies including CGD. To date, haematopoietic stem cell transplantation is the only established option for permanent cure of patients who have a suitable donor, are free of infection and well enough to have a transplant. The genetic modification of the patient own haematopoietic stem cells (HSC), a treatment called “gene therapy” may represent a definitive cure for patients for whom conventional stem cell transplant is not possible.
Two adult CGD patients were treated in Frankfurt with gene therapy in 2004. Both patients showed functional correction of the gene defect and both had a clear clinical benefit from the treatment. However, two severe side effects were observed 5 months after gene therapy: an increase in the number of gene modified cells and secondly, a decrease in the expression of the therapeutic gene. The first side effect observed was caused by the insertion of the gene transfer vehicle (called vector) in close proximity to genes known to be involved in cell proliferation and leukaemia development. The second was caused by down regulation of the therapeutic gene due to silencing of the vector regulatory region important for its expression.
Despite these severe side effects the initial eradication of pre-existing life-threatening infections and other clinical benefits experienced by both patients for more than two years after re-infusion of their own gene modified cells are clear evidence that gene therapy can be an effective strategy for the long-term correction of CGD. However, for future clinical trials, it is essential to develop a protocol that allows a safer and effective gene transfer into haematopoietic stem cells. Over the last five years advances have been made on new gene therapy vectors to improve safety and effectiveness. With CGD RT funding a new, safer, retroviral based vector has been designed and over the last two years work it has been extensively tested in the laboratory and in animal models of CGD with good results. Approval has been gained from the authorities for use of this vector in new clinical trials, that will start in 2011. Planning further ahead, work on the next generation of vectors based on a lentiviral design is being done and these will form the next wave of gene therapy tools from 2013 onwards.
‘The funding provided by CGD RT is crucial in helping us move forward with these developments.'
Professor Adrian Thrasher and Dr Manuel Grez.
TESTING IMPROVED GENE THERAPY VECTORS FOR TREATMENT OF INFECTION AND CHRONIC INFLAMMATION IN CGD
Professor Mary Dinauer
Herman B Wells Centre for Paediatric Research at the Indiana University School of Medicine, USA. $20,000 donation from the Chronic Granulomatous Disorder Association, USA.
This project will test how well the new gene delivery tools for CGD, designed by our researchers at Great Ormond Street and in Frankfurt, will work in animal models. These second generation gene transfer tools are designed for improved safety and for more natural regulation of the X-CGD protein production in white blood cells. Following gene transfer into the blood stem cells of CGD mice, the group will determine the effectiveness of the new tools in improving resistance to fight infections and inflammation caused by the fungi and bacteria such as Aspergillus, Burkholderia cepacia, and Staphylococcus aureus that are threatening to people with CGD. The studies are an essential prerequisite for future clinical trials and will add real value to our gene therapy research programme.
Read interviews with leading researchers on gene therapy
Dr Manuel Grez, lead researcher on the CGD gene therapy project funded by the CGD Research Trust at the Georg-Speyer-Haus Institute in Frankfurt, Germany. http://www.cgd.org.uk/news/news_dr_manuel-grez
Professor Reinhard Seger of the University Children's Hosptial of Zurich. http://www.cgd.org.uk/news/interview_with_professor_reinhard_seger_-_a_leading_clinical_expert_on_cgd__
Previously funded projects - read more...
IMPORTANT NOTE :
The information contained on this website is intended only as a guideline, not as a substitute for medical advice. Always consult your doctor if you or your child has any CGD symptoms or concerns.
© 2001-2007 The Chronic Granulomatous Disorder (CGD) Research Trust
Registered Charity No. 1003425 email:cgd@cgdrt.co.uk
The CGD Research Trust is a member of the Association of Medical Research Charities (AMRC), the Genetic Interest Group (GiG) and an associate member of the International Patient Organisation of Primary Immunodeficiencies (IPOPI)
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