Researchers at the University of Dundee have identified fexinidazole as a possible, much-needed, new treatment for the parasitic disease visceral leishmaniasis.
Leishmaniasis is named after William Leishman, a Glasgwegian doctor serving with the British Army in India, who first identified the parasite in the early 1900s. The disease is the second biggest killer in Africa, Asia and Latin America after malaria, and affects 500,000 people, killing about 50-60,000 patients per year. Current drug treatments for the disease are unsatisfactory for reasons such as high cost, drug resistance or the need for hospitalisation.
Fexinidazole is already in phase 1 clinical trials for a related disease - African sleeping sickness – but a research team at Dundee including Dr Susan Wyllie, Professor Alan Fairlamb and colleagues has identified it as having potential in treating leishmaniasis.
Their research has been published by the journal Science Translational Medicine, and was funded by the Wellcome Trust.
Tests in mice showed that the drug has a greater than 98% rate of suppressing infection of leishmaniasis, comparable to current treatments such as miltefosine and Pentostam.
These and other existing treatment options all suffer from disadvantages; they are not always safe, effective or easy to administer. The only oral drug miltefosine cannot be given to women of child-bearing age due to a substantial risk of birth defects; other drugs are costly and have to be given by injection. Thus there is a continuing need for safe and cost-effective drugs suitable for use in resource-poor settings.
Professor Fairlamb said that fexinidazole has the potential to become a safe and effective oral drug therapy for treating the severest form of visceral leishmaniasis.
"Visceral leishmaniasis is a neglected disease of poverty which causes huge problems across Africa, Asia and Latin America, killing tens of thousands of people every year," said Professor Fairlamb.
"The current treatments are far from ideal and we need to find better, cheaper and more easily delivered drugs to tackle the disease. Our research suggests that fexinidazole has strong potential to do that.
"Drugs for Neglected Diseases initiative have already established that fexinidazole is safe in early clinical trials for African sleeping sickness, so it is some way along the development path.
"This has been a great team effort and I would like to acknowledge the dedication and enthusiasm of the biologists, chemists and pharmacologists involved in this discovery."
Professor Fairlamb and colleagues are based in the College of Life Sciences at Dundee, which houses the Drug Discovery Unit, formed in 2005 specifically to fill the void of research and development of drug targets for diseases of poverty like African sleeping sickness, leishmaniasis, and Chagas' disease that afflict the developing world.
Professor Fairlamb cited the inspiration of the University's former Chancellor, the Nobel prize-winning pharmacologist Sir James Black, in carrying out the research on fexinidazole.
"Sir James always liked to remind me that `the most fruitful basis for the discovery of a new drug is to start with an old drug'. This adage is particularly apt in the search for effective drugs to treat neglected tropical diseases such as visceral leishmaniasis," said Professor Fairlamb. "Indeed, two of the existing anti-leishmanial drugs, miltefosine and amphotericin B, are examples of medicines originally developed for other purposes - anti-cancer and anti-fungal, respectively.
"Our hope is that fexinidazole can follow them and provide relief from a disease that is a major blight across the world."
Notes to editors:
The University of Dundee is renowned for its academic contributions to tropical disease research. Many disciplines towards the discovery of new therapies for tropical diseases are combined, with 76 scientists working in and collaborating with the Drug Discovery Unit.
The Drug Discovery Unit (http://www.drugdiscovery.dundee.ac.uk) within the College of Life Sciences at Dundee has been created to respond to a lack of capacity in the UK for early stage drug discovery in the academic sector. The DDU's aim is to translate basic science into lead compounds to validate putative drug targets, to use as tools to investigate disease pathways and, when appropriate, advance to pre-clinical drug candidates.
The drug discovery programme at the University matches the goals of the Drugs for Neglected Diseases Initiative (http://www.dndi.org), Medicines for Malaria Venture (http://www.mmv.org) and the UNICEF-UNDP-World Bank-WHO Special Programme for Research and Training in Tropical Diseases.
The complete project, from inception and including the construction and equipping of the new state-of-the-art laboratories, is expected to cost around £25 million to 2016.
Investors include the Wellcome Trust, the Scottish Funding Council, The Wolfson Foundation, The European Regional Development Fund, the Drugs for Neglected Diseases Initiative and the University itself.
Roddy Isles
Head of Press
University of Dundee
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E-MAIL: r.isles@dundee.ac.uk
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Journal
Science Translational Medicine