Infectious Disease

Gregory Goldgof, Elizabeth Winzeler and colleagues from the University of California, San Diego in the U.S. have developed a drug-sensitive yeast strain by deleting the main multi-drug export pumps to help identify the mechanisms of action of the 400 next-generation anti-malarial drug candidates in the Malaria Box. This will help optimize drug safety and efficacy for clinical trials. In Phase I, they successfully screened the Malaria Box compounds and identified 30 that were active in their assay.

Lakshminarayanan Ragupathy of HLL Lifecare Ltd. in India will improve the safety and appeal of male condoms by incorporating graphene into existing natural rubber latex condoms. Graphene is a single-layer, crystalline form of carbon that is highly elastic and very strong. And, unlike latex, it also conducts heat. Mixing graphene with existing condom material should lead to stronger, thinner, heat-conducting condoms that are less noticeable for users, and allow for the incorporation of drugs and compounds that can protect against sexually transmitted diseases or enhance sexual experience.

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.

Jacquin Niles of the Massachusetts Institute of Technology in the U.S. is developing a method to switch individual genes on and off in the malaria-causing parasite Plasmodium falciparum for evaluating candidate and existing antimalarial drugs. In Phase I, they built and tested a scalable TetR-aptamer system for rapidly and easily manipulating gene expression in the parasite genome, and showed that it could be used to validate the target of a 4-aminoquinoline antimalarial drug.

Ron Frezieres of the California Family Health Council in the U.S. along with Max Abadi of Unique International in Colombia and I.MAXX Inc. in the U.S. are developing a stronger and thinner male condom made of polyethylene to promote condom use. Polyethylene is a non-toxic and hypoallergenic material that wraps and clings rather than squeezes, thereby enhancing sensation and enabling easier application.

Carl Nathan, Julien Vaubourgeix and Gang Lin of Weill Cornell Medical College will test their hypothesis that tuberculosis is able to exit latency by distributing damaged proteins to a senescent cell lineage, while more functional proteins are diverted to a lineage with full replication potential. Regulating this post-latency cell division could be the target of new drugs. This project's Phase I research demonstrated that M. tuberculosis accumulates irreversibly oxidized proteins when its replication is blocked. These proteins form small aggregates that fuse into larger ones.

Robert Abramovitch of Michigan State University in the U.S. will use their high-throughput drug discovery platform to identify new drugs for treating chronic tuberculosis and for potentially shortening the current treatment time of six to nine months. Their platform exploits a genetic region known as the DosR regulon thought to underlie the behavior of the causative bacteria in humans under low oxygen conditions, when they become dormant and thereby resistant to current drugs.

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.

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.

Joseph Turner of the Liverpool School of Tropical Medicine in the United Kingdom will develop a small animal model of the parasitic disease onchocerciasis, also called river blindness, which is the second leading infectious cause of blindness. Treatment options for filarial infections are currently limited and lack effectiveness. Thus, small animal models of filarial infections are invaluable for preclinical testing of candidate drugs.