Research Leading to Treatment of Widespread Parasitic Disease

A research study led by an Illinois State University professor is moving science a step closer to finding a new treatment for a debilitating parasitic worm disease that affects millions of people worldwide.  The results of that study have are being reported in the advance online publication of the journal Nature Medicine.

David L. Williams, Biological Sciences, along with researchers at the National Institutes of Health (NIH) Chemical Genomics Center (NCGC), have identified chemical compounds that hold promise as potential therapies for schistosomiasis, also known as bilharzia or snail fever.  Williams and his fellow researchers report that chemical compounds known as oxadiazoles can inhibit an enzyme vital to the survival of Schistosoma, a group of parasitic flatworms that cause schistosomiasis.

Of the more than 200 million people affected by the disease, about 20 million people, mostly in tropical areas of the developing world, are seriously disabled due to severe anemia, diarrhea, internal bleeding and organ damage. In addition, another 280,000 people die of the disease each year.

Currently, people living in more than 70 tropical nations require annual or semi-annual treatment with the drug praziquantel to rid their bodies of the parasite.  Public health officials are concerned that the Schistosoma parasites will eventually become resistant to praziquantel and the drug will lose its effectiveness. 

Williams and his team studied Schistosoma maintained in laboratory conditions and found that an oxadiazole compound was effective in inhibiting a crucial worm enzyme, called thioredoxin glutathione reductase (TGR). Furthermore, in tests of laboratory mice infected with Schistosoma, this compound killed the parasite in all of its stages, from larva to adult. The results exceeded all benchmarks set by the World Health Organization for potential new compounds to treat schistosomiasis. The research also showed that the compound was active against all three major species of Schistosoma worms that infect humans.                    

 “This builds upon my lab’s previous findings that Schistosoma worms survive in the host due to a protective enzyme TGR. By teaming with NCGC, we were able to move our research one step closer to the clinic by identifying a class of compounds that specifically target that enzyme,” said Williams. “Still, much remains to be done. Our ultimate goal is to see our basic biological findings translated into help for people with schistosomiasis.”

Williams’ group utilized a high-tech robotic system housed in the labs at the NCGC to quickly screen large numbers of chemical compounds for biological activity.  The technology is part of the NIH’s Roadmap Molecular Libraries Initiative, designed to pursue major opportunities and gaps in biomedical research.  The research team’s efforts were also supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH.

“New therapeutic agents are sorely needed if we hope to ease the burden of schistosomiasis on the world’s health,” said NIH Director Elias A. Zerhouni, M.D. “These findings exemplify what academic researchers can accomplish with access to translational infrastructure and technologies that have previously been beyond their reach.”

People become infected with Schistosoma when they wade, swim or bathe in fresh water inhabited by snails, which serve as the worms’ intermediate hosts. The microscopic worms enter the human body by boring through the skin and migrate into the blood vessels that supply the intestinal and urinary systems. After the worms mature and reproduce, their eggs are eliminated in human urine and feces. If human waste contaminated by worm eggs finds its way into fresh water, the cycle begins again.