Therapeutics/Drugs

R. Paul Johnson of Emory University in the U.S. is using single-cell transcriptional profiling to identify unique biomarkers expressed in CD4+ T cells latently infected with HIV or the simian equivalent SIV. Latent infection of long-lived cells enables the viruses to survive current drug treatments, and makes the disease very difficult to cure. In Phase I, while working at Harvard Medical School in the U.S., they developed a robust high-throughput technique to identify viral genes expressed in single cells and tested it on SIV-infected macaques.

Sara Richter of the University of Padua in Italy will develop a therapeutic to completely clear HIV from the body by targeting a proviral DNA structural motif found in both actively and latently infected host cells. In Phase I they analyzed a highly conserved DNA structural motif of four guanine nucleotides (G-4) found in the integrated HIV-1 proviral DNA and found that it regulates proviral transcription and is likely involved in latent infection.

Euan Wallace of The Ritchie Centre in Australia proposes to test the antioxidant melatonin as a simple and inexpensive intervention to reduce birth-related brain injury.

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.

Vojo Deretic of the University of New Mexico in the U.S. proposed that autophagy, a process by which cells destroy cellular components and intracellular pathogens, can be induced through drug therapy to not only destroy the HIV virus in infected cells, but also to block its transmission from dendritic cells to T cells. This project's Phase I research demonstrated that autophagy can destroy HIV, block dendritic to T cell transfer of HIV, and promote antigen presentation by dendritic cells.

Raffi Aroian of the University of California, San Diego in the U.S. proposes to develop a delivery system for non-toxic, anti-roundworm proteins. With this system, mass production of a safe, potent cure for intestinal Roundworms that is cheap and compatible with global distribution should be possible. This project's Phase I research demonstrated that an anthelmintic protein could be expressed in three food-grade bacterial strains safe for humans.

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.

Ekaterina Dadachova of the Albert Einstein College of Medicine in the U.S., in collaboration with Arturo Casadevall, proposes to use radioimmunotherapy as a strategy to eliminate HIV-infected cells in patients on anti-retroviral therapy. Targeting viral antigens on these cells with radioactivity-armed antibodies could lead to HIV eradication. This project's Phase I research demonstrated that radioimmunotherapy can kill HIV-infected primary human cells in conjunction with anti-retroviral therapy (ART) and that this antibody can also reach HIV-infected cells in the central nervous system.

Filippo Mancia of Columbia University in the U.S. will perform crystallization experiments on a key olfactory receptor used by mosquitoes to detect humans. The aim of these studies is to determine at an atomic level the conserved regions on the olfactory receptor in order to develop drug therapies to block these receptors. This project's Phase I research generated diffraction quality crystals of this targeted mosquito olfactory receptor, and in Phase II, the team will optimize the crystal to determine the structure of the receptor and how it binds to small molecule anti-malarial compounds.

Michelle McIntosh of Monash University in Australia will develop and test the stability and efficacy of a dry powder formulation of the drug oxytocin, which is used to treat post-partum bleeding, in an inexpensive inhalant format that would be a needle-free, non-refrigerated option suitable for use in remote areas with limited training. The project's Phase I research provided proof-of-concept that the inhalation of pharmaceutically engineered particles of oxytocin can rapidly induce therapeutically-relevant contraction of uterine smooth muscle.