Therapeutics/Drugs

Denis Voronin of the Liverpool School of Tropical Medicine in the United Kingdom will identify new drugs for treating common and debilitating human parasitic diseases known as filariasis, which are caused by nematode worms, by specifically targeting their essential bacterial symbiont, Wolbachia.

Richard Komuniecki of The University of Toledo in the U.S. will develop a high-throughput screening platform to identify novel drug targets for treating parasitic nematode (worm) infections, which cause significant morbidity in developing countries. Current drugs are ineffective against some parasitic species, and other species are becoming resistant, thus there is an urgent need for alternative approaches. However, high-throughput drug screens have been challenging because most parasitic nematodes cannot be cultured in the laboratory.

Bryan Bellaire of Iowa State University in the U.S. will improve the safety and efficacy of therapies for treating filarial diseases caused by parasitic nematodes (worms), which are common in developing countries. Current drugs targeting the parasites are becoming ineffective due to the development of resistance, and antibiotics targeting their resident endosymbiont bacteria Wolbachia, which is essential for parasite survival, require multiple dosing regimens that are hard to maintain.

Melvin Reichman of the LIMR Chemical Genomics Center Inc. in the U.S., working with Vicky Avery of the Eskitis Institute for Cell and Molecular Therapies in Australia, will develop and validate a new drug screening approach called Ultra-High Throughput Screening for Synergy (uHTSS) to discover new drug combinations from the Tres Cantos anti-malarial set for the treatment of malaria.

Joseph DeRisi of the University of California, San Francisco in the U.S. will generate a strain of apicoplast-free P. falciparum parasites to identify anti-malarial compounds from the Malaria Box that specifically target this organelle, which is essential for malaria parasite survival.

Choukri Ben Mamoun of Yale University in the U.S. will work to provide proof-of-principle that a new technology for down-regulating the expression of genes in the malaria-causing parasite P. falciparum can be used to identify specific drug targets. Antimalarial compounds in the Malaria Box will be screened against altered parasite strains to determine modes of action and to identify specific cellular targets to be pursued in future drug development.

Manuel Llinás of Pennsylvania State University in the U.S. will characterize the 400 candidate anti-malarial compounds in the so-called "Malaria Box" by mass spectrometry to help select those likely to be the most effective drugs for clinical development. The Malaria Box is a collection of compounds that display some anti- parasitic activity, but how they work and whether they would make valuable new anti-malarial drugs are unknown. They will analyze red blood cells infected with the malarial parasite P.

Dyann Wirth of the Harvard School of Public Health in the U.S. is building a platform to identify combinations of anti-malarial compounds that inhibit the development of drug resistance, which is a major barrier to combatting the disease. Their approach involves predicting how the Plasmodium falciparum malaria parasite will evolve to become resistant to a specific anti-malarial compound, and then designing a second compound that will target these resistant parasites.

Koen Dechering of TropIQ Health Sciences in the Netherlands is developing a high-throughput functional assay to identify new compounds that specifically block transmission of the malaria parasites to their vector hosts, which is a difficult stage to target, and to test candidate drugs. The assay incorporates luciferase- expressing parasites, which emit light as they develop in the mosquito midgut, along with barcoded chemical libraries.

Ronald Quinn of Griffith University in Australia will use anti-malarial compounds as probes to trap protein targets. Mass spectrometry followed by electron capture dissociation (ECD) and electron-transfer dissociation (ETD) will be used to identify individual binding domains between the anti-malarial compounds in the Malaria Box and the malaria parasite proteome that can be used as specific drug targets.