Researchers from both the Texas Biomedical Research Institute and the University of Texas Health Science Center at San Antonio are collaborating along with an international group of scientists in a wide-ranging study on drug resistance to the treatment of Schistosomiasis, a parasitic disease that afflicts over 187 million people in South America, Africa, and Asia. The study, which was led by Texas Biomed’s Tim Anderson Ph.D., and Philip LoVerde Ph.D., from the University of Texas Health Science Center at San Antonio, has revealed that specific genetic mutations result in drug resistance in treating and killing the blog fluke parasite responsible for the disease, a revelation that could positively impact treatment options and drug development.
Claudia Valentim, Ph.D., the primary author of the report and who worked at both institutions, noted that, “This is a major advance,” and explained that, “we were able to identify the critical gene by crossing resistant and sensitive worms in the laboratory and then analyzing the genomes of the progeny. This method is commonly used for fruit flies and other laboratory organisms, but has not previously been possible for schistosome parasites,” according to a Texas Biomed press release.
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Dr. Anderson also noted how the rise of genome sequencing and the critical role that it played in the study’s findings demonstrates its key role in the future of researching, treating, and curing diseases: “This really shows the utility of genome sequencing. The schistosome genome was sequenced in 2009. Without the sequence, the work would have been painfully slow.”
The data and findings from the study, which was funded by the National Institutes of Health (NIH), as well as the WHO and the Wellcome Trust and the Robert A. Welch Foundation is set to debut today in the November 21 online edition of Science.
The Schistosomiasis Scourge
Like so many other neglected tropical diseases that affect a substantial portion of the world populace and yet continues to be largely unaddressed by the medical community, a viable understanding of Schistosomiasis and how to effectively treat it still remains elusive, with researchers in constant need of fresh funding for their research efforts. While perhaps not a common household disease, Schistosome, according to Dr. LoVerde, affects so many people and is the cause of so many unreported deaths, that there is still no definitive number for Schistosome-related fatalities. We don’t know the death toll from these parasites,” says LoVerde, “but our best estimate is that more than 200,000 people die every year from this infection in Africa alone, making this parasitic disease second only to malaria in terms of mortality.”
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Because no vaccine currently exists for the disease, Schistosomiasis can only be controlled in infected patients using drug treatment, reinfection occurs frequently, due to contact with untreated water supplies in the developing world where the intermediate snail hosts of the parasite live. Drug treatment options, however, are limited, and bear mediocre results.
The recent study focused primarily on the drug oxamniquine, a frequently used treatment option that only kills one of the three species of schistosome parasite. In order for a drug like oxamniquine to be truly effective in treating Schistosomiasis, researchers are looking to attenuate the drug so that it kills all three of the parasite species. John Hart, Ph.D., a key collaborator on this study from the Health Science Center, explains: “By using X-ray crystallography and computational methods we were able to precisely pinpoint how the drug interacts with the critical protein in one Schistosome species, and to identify the key differences in this protein in the related parasite species. With some targeted chemical modification, we think it will be possible to make a drug that kills both major schistosome species. This is what we are working on now.”
Oxamniquine is the only viable drug that currently treats schistosomiasis, and in addition to its limited function in killing the parasite species, healthcare providers report drug resistance as well. The findings of the study offer hope for developing new, alternative treatments for schistosomiasis in the near future.
Co-authors on the paper were from Britain, Italy and the University of Texas at San Antonio. They included Frédéric Chevalier, Ph.D., and Marcio Almeida, Ph.D., of Texas Biomed; and Alex Taylor, Ph.D. and Xiaohang Cao, M.D. of the Health Science Center.
This research was supported by NIH grants 5R21-AI096277, 5R21-AI072704, R01-AI097576.