29 September 2004
Potential drug discovery for Leishmaniasis
The scientist who identified the target for several drugs used to treat sleeping sickness and Chagas'
disease has just discovered that antimonial drugs used to treat Leishmaniasis attack the same target.
And, he is "highly optimistic" that research on the parasite molecule "trypanothione", and enzymes that
use trypanothione, will lead to a drug that will cure all three tropical diseases.
Professor Alan Fairlamb at the University of Dundee has worked out how the sulphur containing compound
trypanothione allows these parasites to fend off free radicals and other toxic oxidants produced by the
immune system of the infected patient. Antimonial drugs effectively neutralise the leishmania parasite's
antioxidant defence system, allowing the patient to clear the infection. This may explain why so many
patients co-infected with HIV fail to respond well to treatment with antimonials.
Alan discovered and named the "trypanothione" compound in 1985. Together with his team they have now
worked that trypanothione is vital for parasite survival and now know several enzymes that new drugs will
need to target, including one related to a cancer drug target. The drug discovery and development
process usually takes between 7 and 12 years but Alan believes it will be more rapid once they move the
project into the new Centre for Interdisciplinary Research at the University of Dundee. The new centre,
due to open in 2005 with new facilities in high throughput screening and medicinal chemistry will take
the drug process further than any other UK university can and to a stage where the pharmaceutical
companies will have enough data move it to the production stage.
"Many cases of leishmaniasis in India are now proving resistant to the traditional antimony drugs so new
modern drugs are needed soon", explains Professor Fairlamb. "Resistance to antimonials also involves
trypanothione" and he plans for his team to also investigate how they can use their discovery to reverse
resistance to antimonials until better, safer drugs are developed.
Recent health reports on US soldiers returning home from Iraq with the Leishmaniasis tropical disease has
drawn interest to the killer that has 12 million sufferers worldwide. Commonly brought to the attention
of Western countries after a war, tropical diseases are not well funded by the pharmaceutical industry as
most of their sufferers are in the developing world which is not a profitable market for sales.
Notes for Editors
16 million people worldwide are infected with Chagas disease, 12 million with Leishmaniasis and an
estimated 300,000 with sleeping sickness.
Dundee boasts one of the leading research divisions in Europe studying African sleeping sickness, Chagas'
disease, Leishmaniasis and malaria, who are based in the Division of Biological Chemistry and Molecular
Microbiology in the Wellcome Trust Biocentre. This research will be enhanced in the CIR, which is under
construction and will be joined to and fully integrated with the Wellcome Trust Biocentre. The CIR will
include a new purpose-built Division of Drug Development which will house world-class facilities in
medicinal and synthetic organic chemistry, computational chemistry and compound screening laboratories,
aimed at developing new, safer and more effective drug therapies for the treatment of global parasitic
diseases as well as new treatments for diabetes, cancer and inflammatory diseases.
Information on the CIR fundraising campaign can be found at
www.dundee.ac.uk/externalrelations/funds/index.htm
or by telephoning Joan Concannon, Director of External Relations on 01382 345565 j.concannon@dundee.ac.uk
Notes for Science Correspondents
Details of these discoveries can be found at:
www.jbc.org/cgi/reprint/M405635200v1
www.pnas.org/cgi/reprint/0402918101v1.pdf
www.jbc.org/cgi/reprint/M407958200v1
By Jenny Marra, Head of Press 01382 344910, out of hours: 07968298585, j.m.marra@dundee.ac.uk | 
