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Drug breakthrough in fight against neglected diseases

Scientists have made a major breakthrough in identifying new treatments for human African trypanosomiasis, a fatal disease that infects tens of thousands of Africans each year.

Their findings, made at the Drug Discovery Unit (DDU) at the University of Dundee and published in the latest edition of Nature, describe a new approach to tackling the fatal parasitic disease human African trypanosomiasis, commonly known as ‘sleeping sickness’ because of the disturbance of the sleep cycle caused by parasites infecting the brain. The breakthrough shows promise for the development of effective, orally administered, low-toxicity drugs to treat sleeping sickness.

The compounds developed by the DDU disrupt the enzyme N-myristoyl transferase, or NMT, which is essential for survival and growth of the parasites. It is estimated that drugs could be ready for human clinical trials in approximately 18 months.

‘This is one of the most significant findings made in recent years in terms of drug discovery and development for neglected diseases,’ said Professor Paul Wyatt, Director of the Drug Discovery for Tropical Diseases programme at Dundee. ‘We now have a valid drug target for human African trypanosomiasis and have found leads for drugs which can be dosed orally.

‘Human African trypanosomiasis comes in two stages – we know the drug leads we have identified in this paper can treat the first stage and we are very optimistic that we can now further develop them to treat the second, more serious stage.’

Recent fears over the decreasing efficacy of current stage-two drugs have led the World Health Organization to shift their priorities towards a treatment for the second stage.

The Dundee team worked with partners from the University of York and the Structural Genomics Consortium during the course of the research.

The World Health Organisation estimates that approximately 50,000–70,000 people in sub-Saharan Africa are infected with sleeping sickness, which is spread by the bite of a tsetse fly; however, African sleeping sickness is a neglected disease and has not been on the radar of large pharmaceutical companies.

‘There is little economic incentive for big pharmaceutical companies to engage in diseases from sub-Saharan Africa,’ explained Professor Fairlamb of the DDU. ‘We’ve seen that these companies are now looking to Asia and Latin America as emerging markets, but one doesn’t exist in Africa yet.’

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Pharmacology/ Therapeutics  •  Target Identification/ Validation

 

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