TB kills almost 2 million people a year worldwide, and is increasingly becoming resistant to the antibiotics used to treat it, but there are few new drugs in the pipeline. Doxycycline was introduced in 1967 and is used to treat a wide range of bacterial infections, but until now has not been recognised as effective against TB. The new study, published in the American Journal of Respiratory and Critical Care Medicine, suggests that doxycycline might stop the bacteria from growing and also prevent the disease from damaging the lungs.
Last year, researchers at Imperial College London discovered that TB increases the production of an enzyme called MMP-1, and that this enzyme is responsible for destroying lung tissue.
Now they have found that doxycycline suppresses the production of the tissue-destroying enzyme in TB-infected human cells. They also found that doxycycline directly inhibits the growth of the bacteria in guinea pigs – a surprising result since the drug has been widely used as an antibiotic for over 40 years but has not been considered effective against TB.
“TB treatment has remained unchanged for over 30 years, and totally drug-resistant strains are emerging, so there’s a real need for new drugs.” said Dr Paul Elkington, from the Department of Medicine at Imperial College London, who led the study. “Because doxycycline is cheap, safe and widely available throughout the developing world, it may be a useful new treatment for TB that can be used in resource-poor settings. Our results so far are promising but we have only looked at human cells and animal models. We hope to carry out a clinical trial soon to test whether doxycycline is effective at combating TB in patients.”
The researchers found further evidence for the antibiotic effect of doxycycline in TB bacteria grown in a liquid broth. The higher the concentration of doxycycline, the lower the rate of bacterial growth.
They also studied HIV-infected TB patients in South Africa to look for further evidence that MMP-1 is responsible for destroying lung tissue. They found that concentrations of this enzyme were suppressed in people with advanced HIV infection, explaining for the first time why such patients do not suffer from such extensive lung destruction when they get TB.
The Imperial team worked with collaborators at the University of Cape Town and the Health Protection Agency (HPA) at Porton Down. The research was funded by the National Institute for Health Research (NIHR), the Wellcome Trust, the NIHR Biomedical Research Centre at Imperial, and the HPA.
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Notes to editors:
1. Journal reference
NF Walker et al. ‘Doxycycline and HIV infection suppress tuberculosis-induced matrix metalloproteinases.’ American Journal of Respiratory and Critical Care Medicine, published online 16 February 2012. , doi:10.1164/rccm.201110-1769OC
2. About Imperial College London
Consistently rated amongst the world’s best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 14,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment – underpinned by a dynamic enterprise culture.
Since its foundation in 1907, Imperial’s contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve global health, tackle climate change, develop sustainable sources of energy and address security challenges.
In 2007, Imperial College London and Imperial College Healthcare NHS Trust formed the UK’s first Academic Health Science Centre. This unique partnership aims to improve the quality of life of patients and populations by taking new discoveries and translating them into new therapies as quickly as possible.
3. About the NIHR
The National Institute for Health Research provides the framework through which the research staff and research infrastructure of the NHS in England is positioned, maintained and managed as a national research facility. The NIHR provides the NHS with the support and infrastructure it needs to conduct first-class research funded by the Government and its partners alongside high quality patient care, education and training. Its aim is to support outstanding individuals (both leaders and collaborators), working in world-class facilities (both NHS and university ), conducting leading edge research focused on the needs of patients. www.nihr.ac.uk
4. About NIHR Biomedical Research Centres
NIHR Biomedical Research Centres support research across a wide range of disease areas. These Centres are the most outstanding NHS/University research partnerships in the country; leaders in scientific translation and early adopters of new insights in technologies, techniques and treatments for improving health. To ensure they are able to succeed, the NIHR BRCs receive substantial levels of sustained funding. NIHR BRC funding supports the NHS infrastructure to create an environment where scientific endeavour can thrive, attracting the foremost talent and producing world-class outputs.
5. About the Wellcome Trust
The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust’s breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests. www.wellcome.ac.uk
6. About the Health Protection Agency
The Health Protection Agency is an independent UK organisation that was set up by the government in 2003 to protect the public from threats to their health from infectious diseases and environmental hazards. In April 2013, subject to the usual approvals procedures for establishing new bodies, the Health Protection Agency will become part of a new organisation called Public Health England, an executive agency of the Department of Health. To find out more, visit our website: www.hpa.org.uk or follow us on Twitter @HPAuk.