Gene Therapy
Transplantation
Preventing lung damage
Immunology
Microbiology
Clinical care
Basic science

Gene Therapy
Grant Holder: UK CF Gene Therapy Consortium: Prof. E Alton, Dr U Griesenbach & Dr J Davies (London); Prof. D Porteous & Dr C Boyd (Edinburgh); Dr S Hyde & Dr D Gill (Oxford)
Title: Phase 2 Clinical Study for Wave 1 Gene Therapy product
Term/Award: 01.04.11 - 31.03.14
Institute: Imperial College, London; University of Edinburgh; University of Oxford

Transplantation
Grant Holder: Dr A Fisher
Title: The Role of Ex-Vivo Lung Resuscitation and Anti-inflammatory Secretory Leucoprotease Inhibitor (SLPI) Therapy in Transforming Unusable Donor Lungs for Effective Use in Human Lung Transplantation.
Term/Award: 01.07.08 - 30.06.12
Institute: Newcastle University

Receiving a lung transplant offers real hope to people with Cystic Fibrosis, improving their quality of life and enabling them to plan for the future. In spite of this, nearly half of all people with CF on the waiting list will die before they receive a lung transplant. The main problem is that three-quarters of available donor lungs in the UK are considered unusable due to poor function. This study will assess ways to make donor lungs suitable for transplantation.

A simultaneous study will treat rats with SLPI, a natural anti-inflammatory protein, to see if it protects inflamed donor lungs from poor function after transplant. If this research is successful, it can then be tried in human donor lungs.

Grant Holder: Dr A Fisher
Title: Donor Ex-vivo Lung Perfusion in UK Lung Transplantation - (DEVELOP-UK)
Institute: Newcastle University (with Papworth, Birmingham, Manchester and Birmingham)

The DEVELOP-UK is an internationally important study. The results have the potential to change the way lung transplantation is performed in the UK and more widely by increasing the supply of donor organs for lung transplantation and by tackling the tragedy of patients dying while awaiting lung transplantation. At the end of the study more than 100 patients who may not have received a donor lung otherwise will have has access to lung transplantation and the opportunity for a longer and healthier life.

Preventing lung damage

Grant Holder: Prof. Janet Stocks (UCL) & Prof. A Bush (Royal Brompton)
Title: Early detection of lung disease in infants with CF diagnosed by newborn screening using objective, standardised measures of infection, inflammation, lung structure and function.
Term/Award: 05.01.10 - 04.01.13
Institute: University College London

Keeping lungs free from damage or infection is a priority for people with Cystic Fibrosis. Early diagnosis is vital in ensuring that treatment can begin as quickly as possible. This study will look at the treatment and impact of treatment received by babies who are diagnosed with CF. The research team will investigate lung function, structure and inflammation in babies diagnosed with CF by newborn screening to look at whether there are any signs of infection or inflammation by the time they are one year old.

Grant Holder: Prof. Janet Stocks & Prof. A Bush
Title: From strength to strength: Can we sustain normal lung function in cystic fibrosis newborn screened babies for the first two years of life?
Institute: University College London

This study will follow the progress of the infants from the study above to establish whether lung function at age one year is predictive of that 12 months later.

Grant Holder: Prof. Chris Taylor
Title: Combination of lung MR imaging with physiological assessment to identify and monitor ventilation heterogeneity in early CF lung disease
Institute: Sheffield Children's Hospital

Conventional lung function tests aren't sensitive enough to detect the early signs of infection or inflammation. Because of this, two cutting-edge technologies have been developed to measure changes in gas distribution in the airways, one of the earliest consequences of CF lung disease. These techniques - multiple breath wash-out (MBW) and 3He gas MRI (3HeMRI) - indicate pre-clinical signs of disease of the small airways. This study will combine these technologies to identify and measure the progression of lung disease and compare them with CT, the current imaging gold standard. We hope to show that MBW and 3HeMRI can be used to assess response to new treatments.


Immunology
Grant Holder: Dr Dean J Naisbitt
Title: A prospective investigation of β-lactam allergy in patients with cystic fibrosis to define drug immunogenicity
Term/Award: T.B.A
Institute: University of Liverpool

Adverse reactions to medicines, like antibiotics, can be unpredictable. This study looks at the ways in which drugs inadvertently activate the patient's immune system with respect to B-lymphocyte antibody production, T lymphocyte responses and the activity of regulatory T-cells in patients receiving multiple courses of an important and widely-used drug in respiratory medicine, piperacillin. The findings of this research will also be applicable to other antibiotics. By understanding what triggers an immune response, and whether patients can be desensitised, this study could lead to the development of diagnostic tests that support active patient management strategies.

Microbiology
Grant Holder: Dr Alan Brown
Title: The impact of diabetes on the microbiology of cystic fibrosis lung disease
Term/Award: 01.08.10 - 31.07.13
Institute: University of Exeter

People with Cystic Fibrosis often suffer from serious lung infections caused by a group of bacteria called the Burkholderia cepacia complex (Bcc), which can reduce lung function and life expectancy. In addition, as CF patients get older they frequently develop diabetes, which can make their lungs even less efficient. This research will reveal the direct impact that diabetes has on the Burkholderia infections of the CF lung, and help guide the most effective management of CF-related diabetes.


Clinical care

Grant Holder: Dr A Duff
Title: UK Prevalence and impact of depression and anxiety in people with CF and their caregivers.
Term/Award: 19.10.09 - 18.10.12
Institute: Leeds Teaching Hospitals NHS Trust

Evidence suggests that depression may have a significant impact on health outcomes, including adherence to medical treatments, utilisation of health care services, and rates of morbidity and mortality. This international project will determine whether or not routine screening would contribute to improving health outcomes for people with CF, given the recent NICE guidelines of the effective treatment of depression and anxiety via psychotherapy (cognitive behaviour therapy), and pharmacology.

Basic science
Grant Holder: Prof. Robert Ford
Title: Structure/function studies of full length CFTR after purification and reconstitution into lipid bilayers and vesicles
Term/Award: 01.01.11 - 31.12.13
Institute: University of Manchester

Cystic fibrosis is one of the most common inherited diseases, with about one in every 25 people carrying an altered copy of the gene CFTR. The gene makes a protein which acts as a channel through which chloride ions pass out of the cell. When mutated, CFTR no longer functions properly, and this leads to a series of symptoms, the most serious of which is damage to the lungs. This study will help to understand the structure of the CFTR protein. It might also be possible to develop new drugs to combat cystic fibrosis, or at least better understand how the drugs currently in development work.

Grant Holder: Dr David Sheppard
Title: Drug therapy for cystic fibrosis: mechanistic studies of dual-acting small molecules
Institute: University of Bristol

The proposed research aims to promote the development of new drugs to treat defects at the root of cystic fibrosis (CF). Some drugs called CFTR correctors allow the CFTR protein to be made correctly and delivered to the cell border. Other drugs called CFTR potentiators repair defects in chloride transport, allowing chloride to stream across cell borders. Previous studies have identified drug-like chemicals that act as both CFTR correctors and CFTR potentiators. The aim of this research is to understand better how these chemicals work and improve their design. The findings will inform the development of drug therapies with maximal clinical benefit to CF patients.