Funded in 2006
How does Gamma-Interferon work to improve resistance to infection in CGD?
Professor Jerrold Weiss
Department of Medicine, University of Iowa. £34,000 over one year.
The major clinical problem in CGD is increased susceptibility to certain bacterial infections due to reduced anti-microbial activity of specialized white blood cells. Many CGD patients in the USA receive gamma-interferon on a continual basis and this significantly reduces the frequency of serious bacterial infections. However, how this treatment actually works is not completely understood. This project will help find out more about the anti-microbial pathways affected by gamma interferon so that new and better treatments can be developed to fight infections caused by the rise of multi-drug resistant strains of bacteria. This work will add considerably to our understanding of how gamma interferon works and help increase the armoury of drugs to fight infections in patients who have immune systems that do not work properly.
“I am delighted to receive support from the CGD Research Trust to study how gamma interferon works to improve resistance to infection in CGD. We are hopeful that our studies will provide new insights on the role of gamma interferon in amplification of host defenses against infection that could translate to even more effective treatment in the future. I am particularly happy to have work supported by the CGD Research Trust, a charity that has stimulated efforts to better understand and treat CGD.”
Professor Jerrold Weiss
INVESTIGATION OF CHRONIC INFLAMMATION IN CGD
Professors David. Goldblatt, Christine. Kinnon, and Adrian Thrasher
Institute of Child Health, London
Two Year Project Grant: £109,682, ended in 2005
Patients with CGD can now overcome many infections with new antibiotics, but inflammation can have a serious impact on their quality of life. This project studied the mechanisms involved in causing tissue inflammation and granulomas (abscesses) in CGD patients. The group examined the mechanisms behind the lack of production of certain key anti-inflammatory factors in CGD cells and investigated if specific drugs affected their production. This work provided key insights into why inflammation persists in CGD.
WHAT CAUSES PERSISTENT INFLAMMATION IN CGD?
Professors D. Goldblatt, C. Kinnon, and AJ Thrasher.
The Institute of Child Health, London
2 1/2 -Year Project Grant: £97,476 ended in 2002
This project studied the mechanisms involved in tissue inflammation and granuloma formation in CGD patients. Inflammation can affect various tissues, including the lungs, liver, joints and gastrointestinal tract. Normally, the inflammation occurs when the patient’s cells fight infection. Once the infection has been eliminated the inflammatory process is turned off through the production of specialised anti-inflammatory chemicals. CGD patients appear to lack the means to ‘switch off’ the inflammatory reactions, so those sites of inflammation continue to build up and become granulomas, or abscesses. Significantly this study found that CGD phagocytes, the cell type responsible for the killing and the clearing of bacteria and fungi, produce less of two key anti-inflammatory molecules compared to normal cells. It is thought that the deficient production of these factors leads to the inefficient clearing of cellular debris from the site of inflammation. This continual presence of the uncleared remains of cells then leads to a prolonged inflammatory response. By defining this aberrant production of anti-inflammatory molecules in CGD it is hoped that novel treatments can be better tailored to specifically treat inflammation in CGD patients.
DEVELOPING METHODS TO FIND OUT WHICH PARTS OF THE KEY ENZYME AFFECTED IN CGD MAY CONTROL THE PRODUCTION OF INFLAMMATORY MOLECULES
Dr Dean Willis.
University College, London
1 Year Award: £27,000 ended in 2003
CGD patients have a dysfunction in parts of the enzyme, NADPH oxidase that is important in killing invading microorganisms. Persistent inflammation is a common occurrence in CGD and it is important to find out ways in which this abnormal inflammation can be switched off. In this pilot study, a new method of investigating the role of NADPH oxidase in controlling inflammation was developed that uses ‘RNA interference’ to inhibit the specific function of parts of this important enzyme in CGD. In ‘proof of principle’ experiments specially designed reagents were used successfully to inhibit the function of specific parts of the oxidase enzyme. This new method may help dissect out and unravel the precise roles of key parts of the NADPH oxidase enzyme and could help highlight possible ways by which chronic inflammation can be controlled.
STUDYING INFLAMMATORY BOWEL DISEASE AND TISSUE INFLAMMATION IN CGD
Dr Marcus Harbord and Professor Anthony Segal
University College, London
3 Year Project Grant: £210,000, ended in 2002
Inflammatory bowel disease can be a recurrent and severe problem in CGD. This team investigated a possible association between p47phox pseudogenes and inflammatory bowel disease. This helped improve the understanding and treatment of this unpleasant and painful condition.
EVALUATION OF GRANULOMA FORMATION IN CGD
Professor A Rosen-Woolf, H. von B. Bernuth and J Roesler
Dresden University, Germany
1 Year Award: £20,000, ended in 2002
One of the problems that CGD patients face is the formation of granulomas (abscesses). These form when cells do not die as they should and cause sites of inflammation. In this one-year grant a laboratory model of granuloma formation was established. This allowed a time-lapse study of the formation of this inflammatory tissue to be examined. The group were able to determine the profile of growth mediators at different stages of formation of the granuloma tissue and show that an over abundance of pro-inflammatory factors actively promotes granuloma formation.
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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