Strategic Research Centre: An evidence-based preclinical framework for the development of antimicrobial therapeutics in CF (PIPE CF)
This Strategic Research Centre will lay important foundations for the best way to accurately test the effectiveness of new antibiotic medicines for CF lung infections. The SRC is co-funded between the Trust and the CF Foundation in the United States.
Summary
People with CF spend a lot of time each day taking antibiotics and other medicines to stay well. From time-to-time they get a sudden worsening of their lung health (an exacerbation), which is treated with extra antibiotics. When this happens people may need time off school or work and will feel unwell from the infection and the medicines themselves.
Current treatments for infections are becoming less effective as the infection-causing bugs are developing resistance to them. New, more effective treatments with fewer side effects are urgently needed.
The aim of this Strategic Research Centre is to make it easier for researchers to develop new antibiotics specifically designed to treat CF lung infections. They will do this by creating and checking new methods to test the effectiveness of new medicines. These could be used by university and industry-based researchers around the world.
Background
There are two steps for the development of new medicines in the laboratory. The first step is finding that a chemical or compound could have potential benefit as a new medicine. Sometimes this stage is known as the ‘discovery phase’. The second step is converting that promising chemical into a new medicine. This is usually known as the ‘pre-clinical phase’ of development of a new medicine. If the results of the pre-clinical phase of testing are positive, the medicine will then be tested in clinical trials.
When a new medicine is given approval by the regulators for people to use it, the regulators use both information from the clinical trials and information from the ‘pre-clinical’ tests to make their decision.
The pre-clinical phase of medicine development is slow, expensive and the failure rate is high. As no single laboratory test can mimic everything that may happen in humans, many different versions of these tests are completed to be as sure as the researchers can be that the medicine will be safe and effective in humans.
For many new medicines, the tests to use for the pre-clinical stage of development have already been worked out and accepted by the regulators. This means that taking new medicines through this stage of development can be relatively rapid and cost-effective. However, standardised methods for the testing of new antibiotic medicines to treat CF lung infections have not been developed or approved by the regulators. This represents a significant hurdle for researchers in terms of time and cost.
Aims of the project
The Strategic Research Centre will develop and check a new set of pre-clinical tests specifically to assess the effectiveness of new antibiotic medicines for CF. The aim is that the use of these new tests will make it quicker and easier for researchers to develop new CF medicines in the future.
The SRC research will include investigations into the following:
- Choosing the most representative ‘strains’ of bacteria to include in the tests
- Developing tests to mimic how different infection-causing bugs work together in the CF lung. Many different bugs live within the CF lung and they can all influence each other, so drug developers need to keep this in mind.
- Predicting how individuals with CF would respond to infection, in laboratory tests. This will be done by looking at how new medicines could work in harmony with people’s immune response. The immune response is the body’s self-defence system which fights infections.
- Adapting tests to assess the best dose of the new CF medicines There are no lab tests to specifically work out the best dose to use for new antibiotic medicines in CF. The researchers will adapt a novel method for assessing the dose for antibiotics for other conditions to mimic the environment within the CF lung.
Principal investigator: Dr Jo Fothergill, University of Liverpool
Co-Investigators
- Professor Miguel Camara, University of Nottingham
- Dr Dan Neill, University of Liverpool
- Professor Marvin Whiteley, Georgia Institute of Technology,
- Professor Eshwar Mahenthiralingam, University of Cardiff
- Dr Shampa Das, University of Liverpool
- Professor Andres Floto, University of Cambridge
- Professor Craig Winstanley, University of Liverpool
- Professor Aras Kadioglu, University of Liverpool
- Professor Roger Levesque, Institut de biologie Intégrative et des systems, Quebec, Canada
- Dr Nuno Oliveira, University of Cambridge
- Dr Dilip Nazareth, Liverpool Heart and Chest Hospital
- Professor Andrew Jones, Manchester University Hospitals NHS Trust
- Dr Freya Harrison, University of Warwick