The Wellcome Trust, one of the world’s largest medical charities, has awarded £8.1 million over 5 years to a team of six scientists at the University of Dundee to help discover new drugs to treat some of the world’s most neglected tropical diseases.
The grant awarded to Professor Mike Ferguson, Professor Alan Fairlamb, Professor Bill Hunter, Professor Ian Gilbert, Professor Julie Frearson and Dr Daan van Aalten, all based within the School of Life Sciences at the University, is among the largest given by the Wellcome Trust.
The scientists’ goal is to translate basic research discoveries into candidate drugs ready for clinical trials. The diseases, which include African sleeping sickness, Chagas’ disease and leishmaniasis, are among the most neglected in the world, affecting millions of the world’s poorest people and attracting little or no interest from pharmaceutical companies.
"Sleeping sickness is endemic in sub-Saharan Africa and is fatal if not treated, but the front-line arsenical drug, melarsoprol, is so poisonous that it kills 5% of patients receiving treatment," said Professor Fairlamb, who is leading the project with Professor Ferguson.
"Chagas’ disease is a silent killer; patients are often unaware of being infected but about 15% of them will die prematurely from heart failure or other complications. The existing drugs are toxic and only cure some patients in the early stages of infection.
"The leishmaniases are a set of diseases ranging from nasty skin infections - oriental sore - to grossly disfiguring infections that eat away the nose and mouth – espundia - or to fatal infections of the liver, bone marrow and spleen - kala azar. Again, the existing drugs leave much to be desired and drug resistance is a major problem. "
There are over 140,000 reported deaths from these diseases each year, but it is generally agreed that this is an underestimate because of the lack of medical reporting in many under-developed countries.
The gap between basic research in academic laboratories and applied research in the drug industry has widened considerably in this area over the last decade. The Dundee scientists aim to bridge this gap by embarking on a programme to exploit ‘drug targets’ already discovered in their basic research by adding industry-style compound screening and medicinal chemistry.
"This initiative aims to marry the best of drug industry practice with academic excellence in a University environment," said Professor Ferguson.
The parasites causing these diseases are protozoan microbes spread by blood-sucking insects, and afflict millions of people. The World Health Organisation (WHO) estimate that;
- there are around 400,000 cases of tsetse fly-transmitted African sleeping sickness each year.
- more than 16 million people have Chagas’ disease (endemic in South and Central America)
- more than 12 million have leishmaniasis (a range of diseases found throughout the tropics and sub-tropics).
No vaccines exist to prevent these debilitating and often lethal infections. Many of the current drugs have serious side effects and would not meet current standards for safety and efficacy. Others are either too expensive for widespread use or becoming less effective because of resistance.
The University of Dundee team are renowned for their academic contributions to tropical disease research. Together, they integrate many disciplines directed towards the discovery of new therapies for tropical diseases.
The £8.1 million grant will allow them to add a team of 16 scientists to their existing 60 and to span all the disciplines needed to go from biology to drug design, synthesis and testing. The new activities will be housed in the newly completed Centre for Interdisciplinary Research at the University, a £20 million building specialising in tropical disease research, diabetes and cancer. Professors Ferguson said, "We are delighted with the enthusiasm, good-will and financial support we have received from The University and the Wellcome Trust to get this underway. This initiative will have a major impact on those suffering from these appalling diseases."
The total project, including the construction and equipping of the new state-of-the-art laboratories, will cost about £13 million over the next 5 years. While the lion’s share of the additional research and development activity will be met by the Wellcome Trust award, very significant investments in infrastructure and academic appointments have been made by The University of Dundee itself, by the Scottish Higher-Education Funding Council (in the form of a strategic research development grant of £1.5 million to Dundee, Glasgow and St Andrews Universities) and by The Wolfson Foundation, who gave £2 million to help construct the new laboratories.
Professor Ferguson commented "Getting all the pieces in place to carry out a serious drug discovery programme in an academic environment is virtually unprecedented and quite demanding. Everyone in the team has done a fantastic job. We all bring different blends of scientific expertise to the project and, most importantly, share the vision of translating our knowledge into new therapies for neglected diseases.
"We are particularly pleased to welcome on board Professor Julie Frearson, recruited from the company Cambridge BioFocus plc, who will set up and oversee our compound screening facility, Professor Ian Gilbert, recruited from Cardiff University, who will supervise the medicinal chemistry, and Dr Ruth Brenk, recruited from The University of California, San Francisco, who will bolster our computational chemistry and drug design."
Dr Mark Walport, Director of the Wellcome Trust said, "Many drugs currently used to treat important diseases in the world's poorest countries, such as sleeping sickness and leishmaniasis, are no longer effective and may have serious side effects.
"We hope that this exciting project will translate the insights arising from basic research into new or improved treatments for the millions of people whose lives and livelihoods are threatened daily by tropical infectious diseases.
"Wellcome Trust funding is bridging a wide funding gap in the UK allowing health researchers involved in early-stage drug discovery projects to advance promising innovations to a stage where they become attractive to public/private partnerships and the commercial sector for further development."