Search for new drugs for malaria and African sleeping sickness
Parasitic diseases are still posing a significant threat to human health mainly in developing countries. Malaria, forming together with HIV/AIDS and tuberculosis the ‘big three’ of infectious diseases, is responsible for some 250 Million malaria episodes and over 800’000 deaths annually.1 Other important diseases caused by protozoan parasites are human African trypanosomiasis (sleeping sickness), Chagas disease and visceral leishmaniasis. All three diseases are potentially fatal and cause approximately 100’000 deaths annually. The drugs available for these diseases are mostly old, lack efficacy or suffer from drug resistance, show side effects and require long or complicated treatment.2,3 For African sleeping sickness an arsenical drug (melarsoprol) was used until recently which killed approximately 5% of the treated patients. There is an urgent need for new safe, effective and affordable medications which are easy to administer.
Ten years ago the WHO, not-for-profit and philanthropic organizations initiated product-development-partnerships (PDPs), such as the Medicines for Malaria Venture foundation (MMV) or the Drugs for Neglected Diseases initiative (DNDi). Bringing together partners from academic and governmental institutions, as well as biotech and pharma companies, a new model of R&D for new drugs was established. At the Swiss Tropical and Public Health Institute a Screening Centre for protozoan parasites is operating which collaborates with such PDPs and many other partners. Research endeavours during the last 10 years resulted in several molecules that are in clinical studies or will soon enter phase I trials: For malaria two new clinical candidates were recently selected, the spiroindolone NITD6094 and the synthetic peroxide OZ4395. For human African trypanosomiasis (sleeping sickness) the nitroimidazole fexinidazole6 entered phase II clinical trials while two other chemical classes i.e. aromatic diamidines7 and benzoxaboroles7 are in the pipeline as back-up molecules. It is our great hope that in a few years a new drug for malaria and one for sleeping sickness will be available to complement the treatment options for malaria and to assist the elimination of sleeping sickness.
2 Nwaka S, Hudson A. Innovative lead discovery strategies for tropical diseases. Nature Reviews Drug Discovery 5:941-955 (2006).
3 Renslo AR, McKerrow JH. Drug discovery and development for neglected parasitic diseases. Nature Chemical Biology 2:701-710 (2006).
4 Rottmann M, McNamara C, Yeung BK, et al. Spiroindolones, a potent compound class for the treatment of malaria. Science 329:1175-1180 (2010).
5 Charman SA, Arbe-Barnes S, Bathurst IC, Brun R, et al. Synthetic ozonide drug candidate OZ439 offers new hope for a single-dose cure of uncomplicated malaria. Proc Natl Acad Sci USA 108:4400- 4405 (2011).
6 Torreele E, Bourdin Trunz B, Brun R, et al. Fexinidazole - a new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness. PLoS Neglected Tropical Diseases 4:e923 (2010).
7 Brun R, Don R, Jacobs RT, Wang MZ, Barrett MP. Development of novel drugs for human African trypanosomiasis. Future Microbiology 6:677-691 (2011)
Saarland University, Campus Bldg. B2.1, 002
Reto Brun, Swiss Tropical and Public Health Institute, Basel
Rolf Müller (HIPS-MINS)