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Sleeping sickness is a common African disease which already exists since at least the fourteenth century. In some regions of sub-Saharan Africa it is even endemic. It affects about 36 countries.
The disease is caused by a parasite, Trypanosama bruccei, which is transmitted by the sting of the tsetse fly. The disease goes unnoticed as long as the parasites have not reached the brain. This is usually the case in the West-African variant, where it can take years before symptoms start to show. The East African variant is typically more aggressive. When a person is infected with the parasite the skin surrounding the sting swells and gets infected. In this first, haemolymphatic, stage corresponding symptoms include fever, headache, fatigue, swollen lymph nodes and painful joints and muscles. Once the parasite has entered the brain the central nervous system is infected and the disease enters the second, neurological, stage. In this stage sleeping disorders, epileptic attacks, confusion, and numbness may develop. In general, if the patient is left untreated the disease is fatal.
Leishmaniasis is a disease that is mostly prevalent in tropical areas, but also occurs in Mediterranean countries.
The disease is caused by the leishmania parasite, which is transmitted by the sandfly. The visceral form is the most severe, where parasites have migrated to vital organs, such as liver and bone marrow. The incubation period varies between ten days and several years, but generally is two to seven months. It results in fever, weight loss, swelling of the organs, and anemia. If left untreated this form is fatal. Luckily this form is not very common. The most common, and less severe, form is cutaneous leishmaniasis. This is a skin disease where the sting results in ulcers. In the mucotaneous form ulcers appear on the mucous membranes such as nose and mouth, which can deform the entire face.
Trypanosomes contain a phosphodiesterase (PDE) essential for parasite survival and these will be used as targets and screened with various lead compounds known to have inhibitory activity. The compounds are known to be effective against both the Trypanosomiasis parasite as well as the Leishmaniasis parasites.
The aim of this project is to use PDE's as targets and so develop well defined drug candidates in terms of potency, selectivity and stability for the parasites phosphodiesterases and for evaluation in clinical studies of the African Trypanosomiasis and Leishmaniasis.
Full project title: Phosphodiesterase (PDE) inhibitors for Trypanosomiasis and Leishmaniasis
Start date: July 2009
End date: July 2013
Goal: Development of lead candidate compounds specific for these parasites, but selective against the human target PDE
Principal investigator: Rob Leurs, Vrije University Amsterdam
Project size: 19 FTE's
Partners: Mercachem BV, IOTA Pharmaceuticals, Nycomed GMBH, Vrije University Amsterdam, The Dutch Royal Tropical Institute, Drugs for Neglected Disease Initiative, Bern University, TI Pharma