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Potential drug discovery for Leishmaniasis

29.09.2004


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.

Jenny Marra | alfa
Further information:
http://www.dundee.ac.uk

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