Trypanosomatid protein synthesis as a target for novel drug therapies

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Trypanosomatids are eukaryotic parasites that migrate between insect vectors and mammalian hosts. They cause a number of highly debilitating and potentially fatal zoonotic diseases with major impacts on human health (and life-span) on a global scale. Trypanosoma cruzi, which causes Chagas disease, is believed to affect approximately 11 million people in Mexico, Central America and South America. There is currently no vaccine against Chagas disease, and the available antiparasitic treatments are unpleasant and not fully effective. Moreover, resistance to the commonly used azole- and nitro- derivative drugs is rising. Leishmania is spread by sandflies in South America, southern Europe, the Middle East, Asia and Africa, and causes three types of disease (cutaneous, mucocutaneous and visceral leishmaniasis) in approximately 12 million people. Many of the drugs used against Leishmania have side effects, and resistance is on the increase. In this project, we propose to investigate the feasibility of pursuing a new route to developing drugs effective against these dangerous parasites. This route involves differential targeting of the protein synthesis machinery in the parasite so that the human (or animal) host is unaffected.Over the two years of this project we expect to achieve a significantly enhanced level of understanding of important targets for drugs in trypanosomatids and also to have identified some candidate drugs that can be incorporated into trials in animals subsequent to this study.