Improving gene therapy

Professor Adrian Thrasher is developing new gene therapy reagents to treat people with CGD who are unable to have stem cell transplantation because they are too ill or cannot find a matched donor.

Project leader: Professor Adrian Thrasher
Locations: Institute of Child Health, University College London
Researchers employed on project: Dr Giorgia Santilli
Duration: 2 years
Total project cost: £192,781
Official title: Improving gene therapy for CGD: Vector development, testing and clinical application

This project is aimed at developing a cure for CGD by gene therapy. We rely on our genes functioning correctly, so when a gene is missing or not functioning properly, a genetic disease will result. Gene therapy is a way of putting the correct genetic information back into a cell so that it follows a normal healthy set of instructions.

This project is vital for people affected by CGD who cannot find a good match for bone marrow transplant or are too ill to undergo the associated chemotherapy procedures.

Building on previous work funded by CGDS this project will refine and develop new gene therapy tools for treating the most common form of CGD, X-linked CGD. The aim is to improve the safety and effectiveness of gene therapy building on the outcomes and results from previous CGD gene therapy clinical trials.

Gene therapy is emerging as a new branch of medicine for the treatment of inherited disorders such as CGD and is considered the most promising avenue of research to find a cure.

What this research means to people with CGD 

Gene therapy has been shown to save and extend life for people with CGD who are very seriously ill, who have infections that conventional medicines cannot treat and who are unable to have a stem cell transplant.

The work will result in a new gene therapy reagent based on a lentivirus design is currently being tested.  The aim is for this to be in clinic for 2012.

Background information

Work has been progressing on gene therapy for CGD with funding from CGDS from 1997 to the present day. This has resulted in translating experiments done in the laboratory to real tangible benefits for CGD patients.

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 the development of leukaemia. The second was by ‘silencing’ of the therapeutic gene causing it not to work.

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 gene therapy are clear evidence that gene therapy can be an effective strategy for the long-term correction of CGD.

However, for future clinical trials, it was essential to develop a new protocol that allows a safer and more effective gene transfer into CGD patients’ stem cells.  Over the last five years advances have been made on new gene therapy vectors to improve safety and effectiveness.  With CGDS funding the next generation of vectors based on a lentiviral design is being developed. This will form the next wave of gene therapy tools from 2012 onwards. 

Further information and links 

Centre for Immunodeficiency

‘Gene Therapy Cures Immune System Defects’