Therapeutics/Drugs

We will make neutralizing antibodies against antigenic regions of HIV recently identified in rare cases of ""natural resistance"". A key will be to produce antibodies in alpacas because of their properties of simplicity, specificity, size & stability.

Some rare individuals are resistant to HIV infection; their immune system have a phenotype called immune quiescence. We propose to induce immune quiescence in highly susceptible women by using low cost anti-inflammatory drugs to reduce HIV incidence by 30%.

torvastatin study at Makerere University College of Health Sciences to test the role of the drug on HIV-associated immune activation among suboptimal responders to antiretroviral therapy. The drug will help to improve immune recovery among HAART-treated HIV-patients in Africa.

Warwick Grant of La Trobe University in Australia will develop a small animal parasite model to test candidate drugs for treating the parasitic nematode Onchocerca volvulus, which causes river blindness in humans. They will establish infection of the related parasite Cercopithifilaria johnstoni in rats and evaluate the pathology for similarity to the human disease. The model will then be validated for testing human anti-onchocercal drug candidates by analyzing the effect of drugs with proven success in patients.

Tae Seok Moon from Washington University in the U.S. will develop a bacterial-based strategy to block the transmission of soil-transmitted helminth infections (intestinal worms), which occurs via parasite eggs present in human feces. They will engineer consumable probiotic bacteria that are designed to sense when they are excreted from the body and to subsequently release toxic substances designed to kill the parasite eggs in order to prevent disease transmission.

Edward Mitre and his team at the Uniformed Services University in the U.S. will develop a method for the long-term maintenance of parasitic Roundworms (filariae) in cell-free culture. Human filariae cause substantial morbidity worldwide, but current therapies are inefficient or cause harmful side effects. Additionally, the inability to maintain filariae in vitro has hampered screening efforts to identify new drugs.

Aaron Maule of Queen's University Belfast in the United Kingdom will develop food crops expressing microRNAs that, upon ingestion by humans, can be used to target and kill parasitic worms and the mosquitos that transmit them. Plant microRNAs can survive the digestion process and are detected in human blood following consumption. Therefore, they may also be encountered by blood-borne parasitic worms and by the blood-eating insects that transmit them, which cause widespread disease. He will select candidate microRNAs and test their activity using rodent infection models.

Michael K. Chan of the Chinese University of Hong Kong in China and his collaborators will use dawadawa, a staple food in western Africa, as the basis of a novel therapeutic for treating and preventing multiple parasitic worm (helminthic) infections, which are prevelant in developing countries. Dawadawa can be produced by fermenting soyabeans with Bacillus bacteria. By engineering Bacillus to produce parasite-killing (antihelminth) proteins, they can make a staple food with therapeutic properties at low cost.

Janis Weeks and Shawn Lockery of the University of Oregon and NemaMetrix in the U.S. have developed a drug discovery platform that they will tailor to identify new drugs for treating soil-transmitted helminthic (STH) infections, which are caused by parasitic nematodes (worms). STH infections are the most common human infection, causing pain, disability, and even death. However, current treatments are inadequate and due to technological barriers there are no new drugs on the horizon.

Stephen Miller and colleagues at the University of Massachusetts Medical School in the U.S. will identify and characterize molecular features that can easily penetrate Roundworms (nematodes), which commonly infect humans and can cause disability and death. Current treatment options are limited and toxic, and are losing efficacy due to the development of resistance mechanisms that can prevent the drug from entering the worm.