Based on a profound expertise in the in vitro cultivation of protozoan parasites, the group under the leadership of Prof. Reto Brun started to establish a Screening Centre for protozoan parasites at the beginning of the 1990s in collaboration with the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR).

The backbone of the STI Screening Centre was an integrated in vitro screening which tested compounds against African and South American trypanosomes, leishmanias and malaria as well as for cytotoxicity in parallel. Less than one milligram of a compound is needed to get information on the 4 parasites. The principle is a serial drug dilution in 96-well plates with an automatic readout. In vitro active compounds will be forwarded to mouse models of infection, which were established for African trypanosomes and for malaria. An array of different models is available with standard operating procedures (SOPs) and a database with data for all the standard drugs. Regarding the mouse models we can distinguish between acute and chronic models, a single or a multiple application of the compounds, different routes of administration, different parasite strains with different characteristics, etc.

Today the STI Screening Centre employs over 15 people, including a new subunit which is working with helminth diseases (schistosomiasis and food-borne trematodiasis). The group has very tight links to the TDR program ‘Genomics and Discovery Research’, to the Medicins for Malaria Venture (MMV) Foundation and the Drugs for Neglected Diseases initiative (DNDi). Further collaborations exist with several international consortia consisting of partners from universities and from private industry (small and big pharma). The Consortium for Parasitic Drug Development (CPDD) under the leadership of the University of North Carolina and supported by the Bill and Melinda Gates Foundation is exploiting diamidines as new drugs against sleeping sickness. One new product is already in phase III clinical trials for the early stage of this disease and so the effort of the discovery work is now focusing on the second stage of the disease with infection of the brain. Three diamidines could already be identified which cure brain infections in mice. Preclinical work done by our partners in the consortium is dealing with toxicology, pharmacokinetics, metabolism and efficacy in a monkey model. The Bill and Melinda Gates Foundation just awarded another 5 years of funding for the development of a clinical candidate for advanced sleeping sickness.

 

Prof. Dr. Reto Brun
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left: Preparation of an assay in a 96-well microtiter plate with parasites in a serial drug dilution.
middle: Incubation of the assay plate at 37°C for 72 hours.
right: Reading of the plate in a fluorescence scanner with data transfer to our intranet.

 

please click to enlarge