PreDiCT-TB

Tuberculosis (TB) is still a huge global public health issue and the single biggest killer amongst infectious diseases, particularly in developing countries. The treatment usually involves a combination of antibiotics, which poses a problem for companies that are used to developing one drug a time. Additionally, the current laboratory models used to predict the potential of new drug candidates have not been reliable, leading to a high failure rate in clinical trials. PreDiCT-TB project scientists developed a series of tools, which drug developers can use to increase the probability of them choosing the right drug-like compounds and getting them through clinical trials successfully. ###With that, the project laid the foundations for faster and better development of new TB medicines for the benefit of patients. In an interview with the IMI Programme Office, EFPIA project coordinator Justin Green of GSK and academic coordinator Gerry Davies of the University of Liverpool, explain how PreDiCT-TB transformed the tuberculosis field and could speed up the development of new treatments for the benefit of patients. ‘[Our project] changed people’s attitude towards drug development in TB,’ said Davies. ‘Some of the techniques that we brought in are simply best practices in modern drug development and we have applied them to a field in which perhaps that’s been lacking for decades. We can certainly say that some of the tools that we developed – some of the statistical modelling tools and some of the technologies in the lab – have the potential to be transformative.’

• Read the full interview

Current methods of diagnosing tuberculosis (TB) and measuring the effect of potential new treatments in clinical and pre-clinical trials depend on either culturing TB bacteria from a patient-derived specimen, or DNA-based diagnostic tests. Growing a culture is very slow, taking up to three months before a result is available.### DNA tests on the other hand are fast, but they remain positive even after the bacteria is dead, making them unsuitable for tracking the effectiveness of potential new treatments. A new method fine-tuned by the PreDiCT-TB project offers a much faster way to diagnose tuberculosis and has the potential to improve both the speed and effectiveness of preclinical and clinical TB trials. The method is based on measuring ribosomal RNA, which is part of the structure of the organisms’ protein synthesis machinery. The RNA is easy to detect even when there are very few organisms present, and unlike the DNA, it does not survive long after the bug is killed by antibiotics. The method gives an answer in as little as four hours, and might also be able to identify a population of more persistent, antibiotic-resistant bacteria. Although the test was initially developed prior to PreDiCT-TB, the work done within the consortium enabled the creation of a test that is easier to use and is more reliable. 'PreDiCT-TB has increased the speed with which we have been able to apply this test to defined regimens and the consortium has allowed us to draw on the expertise from across the community,' said Justin Green, PreDiCT-TB project coordinator. ‘We believe this test may contribute to the speeding up of the evaluation of new drugs. It also has the potential to improve clinical management of hard to treat patients.’ PreDiCT-TB aims to speed up the search for new, more effective combinations of treatments to tackle TB, and is one of the world’s only initiatives focused on tackling pre-clinical research barriers to the discovery and development of new drug combinations for this deadly disease.

On 24 March, World TB Day, IMI’s tuberculosis (TB) project PreDiCT-TB highlighted how it is contributing to efforts to ‘unite to end TB’ – the motto of this year’s events. According to the World Health Organization (WHO), in 2014, 9.6 million people fell ill with TB and 1.5 million died; most of these cases were in low and middle income countries.### Treatment still requires six months or more of combinations of antibiotics to ensure a complete cure and more effective drugs are urgently needed to shorten treatment. The goal of the PreDiCT-TB consortium is to find the most rapid and reliable ways of identifying the most potent combinations of new drugs and hasten their arrival in the clinic. On World TB Day, PreDiCT-TB published new materials, including articles, videos and images explaining the project’s activities and progress.

Tuberculosis (TB) project PreDiCT-TB marked World TB Day on 24 March with a series of articles, videos and tweets on its activities. TB is an infectious bacterial disease. Although it is both preventable and treatable, in 2013, 9 million people fell ill with TB and 1.5 million died.### The goal of PreDiCT-TB is to find the most rapid and reliable ways of identifying the most potent combinations of new drugs and hasten their arrival in the clinic. Material released on World TB Day included:

• An article on the University of St Andrews’s work in the project. The team looks at ways of detecting TB bacteria that are naturally resistant to current treatment and using this information to understand and predict the effect of current and future treatment regimens.
• Videos from the team at the University of Liverpool, including an overview of the project and a discussion on historical clinical trial data.
• A day in the life of Sanofi’s Lucie Eckenberg-Friedlander, who heads up the project’s work package on data management.
• An article on the team at École Polytechnique Fédérale de Lausanne (EPFL), which is developing tools to assess the efficacy of TB drugs.
• An interview with the project’s academic coordinator, Dr Gerry Davies of the University of Liverpool.

IMI’s PreDiCT-TB and C-Path’s CPTR projects have signed a Memorandum of Understanding to coordinate their work in developing new and effective treatment regimens for tuberculosis (TB).### TB is a leading cause of death worldwide, with nearly 9 million new cases and 1.4 million deaths reported every year. A major challenge for those tackling the disease is the length of TB treatment – even standard cases require at least six months of treatment with a multi-drug regimen, while drug-resistant strains of the disease can take two years to treat. Both PreDiCT-TB and CPTR are working to speed up the development of shorter, more patient-friendly treatment regimens. By working together, the teams will be able to combine their forces to take on the challenges in this area more effectively.