Therapeutics/Drugs

S.K. Dey of Cincinnati Children's Hospital Medical Center in the U.S. will test the hypothesis that the protein mTor, which regulates cell growth and survival, plays a critical role in premature uterine aging that lead to preterm birth, difficult labor and fetal death. This research could lead to the development of new strategies to combat preterm birth.

Beth Kolko of the University of Washington in the U.S. will build on recent research that has revealed that current portable ultrasound devices are often too complex for rural midwives in developing countries to use, and will develop instead a streamlined, inexpensive device with limited functionality, a simplified user interface, and a contextual help system. The prototype will be field tested with midwives in Uganda.

David Clapham of Boston Children's Hospital in the U.S. will develop and test a nanoparticle contraceptive that releases sperm tail inhibitors in response to vaginal pH changes or exposure to prostatic fluid. The nanoparticles could be incorporated into a vaginal gel to block sperm motility required for fertilization. This project's Phase I research culminated in the development of mesoporous silica nanoparticles that contain sperm inhibitors.

Renjie Chang of Lavax in the U.S. will develop and test a vaginal suppository that uses a strain of commensal bacteria which has the ability to immobilize sperm and capture viruses. If successful, the bacteria could be used as a reversible contraceptive that also affords protection against viruses such as HIV and herpes.

Samuel Wickline of Washington University in the U.S. will formulate a vaginal gel that contains nanoparticles which serve as decoys to attract both sperm and HIV. The nanoparticles will fuse with specific receptors in the sperm and virions, causing both to deliver their genetic material into the nanoparticles, which simultaneously delivers a peptide that incapacitates both targets.

Melissa J. Moore of the University of Massachusetts Medical School and S. Ananth Karumanchi of Harvard Medical School in the U.S. propose to develop siRNA- based therapies to silence genes in the placenta which produce excess proteins that cause preeclampsia. Temporarily silencing these genes can prolong pregnancy and protect the life of both infant and mother. In Phase I, they demonstrated that siRNAs can be delivered to the placenta, and those designed to target the mouse versions of soluble fms-like tyrosine kinase-1 (sFlt1) could safely decrease protein levels in pregnant mice.

John Herr of the University of Virginia in the U.S. will research the egg-specific membrane enzyme metalloprotease as a target for a non-hormonal female contraceptive. After determining the nature of the enzyme's catalytic pocket, a family of peptidomimetic compounds will be tested for their ability to bind to the enzyme and block its key role in egg fertilization.

Haim Breitbart of Bar-Ilan University in Israel will design and test antisense molecules that will inactivate specific genes within sperm that are essential to the fertilization process. If successful, these antisense molecules can be used to develop a reversible oral male contraceptive.

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.

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.