Therapeutics/Drugs

Kaveh Ashrafi of the University of California, San Francisco in the U.S. will use the free-living model nematode worm Caenorhabditis elegans as a molecular platform to identify new drugs capable of killing adult filarial parasitic worms, which cause serious infections. C. elegans is a non-parasitic model organism that can be easily grown and manipulated in the lab, unlike related parasitic Roundworms. Ashrafi will genetically engineer C. elegans to carry the parasitic version of the gene encoding phosphodiesterase-4, inhibition of which is known to kill the parasites.

Mostafa Zamanian of Iowa State University in the U.S. will take schistosomes, which are parasitic worms that cause a range of infectious diseases, make them sterile, and genetically modify them to deliver anti-parasitic (anthelmintic) agents into humans to protect them against subsequent infections. They will use genome editing, guided by RNA in the worms, to disrupt individual genes required for laying eggs in order to make the worms sterile and thereby non-pathogenic.

Cecilia Bouzat of the Instituto de Investigaciones Bioquímicas de Bahía Blanca in Argentina will develop a drug screening platform to identify new antiparasitic drugs using the model nematode Caenorhabditis elegans. There are limited numbers of effective anthelmintic drugs and resistance to these drugs is emerging in the field. However, parasitic nematodes are unsuitable for large-scale drug screens mainly because they generally require host animals to survive. She will use the related free-living C.

Edward Mitre and colleagues at the Henry M. Jackson Foundation for the Advancement of Military Medicine in the U.S. will develop a short course therapy for clearing adult filarial worms, which cause substantial morbidity and mortality, to enhance eradication efforts. Current antifilarial medications target only larval forms of the worms, requiring repeated administration until the natural death of the adults. Filarial infections are known to induce immune cells to release histamine, which can regulate the immune response.

Renato Luis da Silveira Ximenes of Universidade Federal de São Paulo in Brazil will conduct a randomized controlled trial to evaluate whether a daily low dose of aspirin taken from early in pregnancy can prevent preeclampsia and thereby reduce the rate of preterm birth. Preterm birth is a leading cause of neonatal morbidity and mortality, and preeclampsia is a major cause of maternal death.

Jianjun Sun of the University of Connecticut in the U.S. is developing non-hormonal contraceptives using a fly-based ovulation assay to identify compounds that specifically block the rupture of follicles, which is required to release eggs for fertilization also in mammals. The popular female contraceptive "pill" alters the hormonal cycle and is widely used throughout the Western world. However, it can have undesirable side effects.

William Witola of the University of Illinois in the U.S. will help develop new drugs for treating children infected with the protozoa Cryptosporidium by using a gene knockdown approach to evaluate candidate drug targets. Found in contaminated water, Cryptosporidium is the second most common cause of potentially lethal diarrhea in young children in developing countries. There are no safe and effective drugs available due largely to the lack of genetic tools for studying Cryptosporidium in the laboratory.

Christopher Huston of the University of Vermont in the U.S. will screen for compounds that inhibit differentiation of Cryptosporidium in culture in vitro. Lack of a continuous in vitro culture system impedes drug development for Cryptosporidium, which causes substantial morbidity and mortality in developing countries. Cryptosporidium infects intestinal cell lines but it quickly differentiates from replicating asexual to non-replicating sexual forms.

Timothy Geary at McGill University in Canada proposed screening chemicals derived from the biological diversity found in Africa to identify lead compounds for the development of drugs to treat infections caused by parasitic nematode worms. In this project's Phase I research, Dr. Geary established drug discovery centers at the Universities of Botswana and Cape Town, South Africa to screen for compounds that target a nematode family of peptidergic G Protein-coupled receptors. In Phase II, the team is expanding the screening efforts.

Timothy Geary at McGill University in Canada proposed screening chemicals derived from the biological diversity found in Africa to identify lead compounds for the development of drugs to treat infections caused by parasitic nematode worms. In this project's Phase I research, Dr. Geary established drug discovery centers at the Universities of Botswana and Cape Town, South Africa to screen for compounds that target a nematode family of peptidergic G Protein-coupled receptors. In Phase II, the team is expanding the screening efforts.