The flatworm that causes the tropical disease schistosomiasis has a newly discovered Achilles’ heel that drugmakers might be able to exploit.
The target is an enzyme called thioredoxin glutathione reductase (TGR). Biochemist David L. Williams of Illinois State University in Normal, and his colleagues identified the enzyme in the Schistosoma mansoni worm in earlier research.
To test TGR’s importance to the parasites, the researchers grew larvae in the lab and inserted fragments of RNA that would stop the enzyme’s production. The procedure killed the larvae, the researchers report in the June PloS Medicine.
Next, the scientists tested two old schistosomiasis drugs—including an antimony-based compound—that are no longer prescribed because of their side effects. Both drugs neutralized TGR in lab-dish tests.
A third drug, a gold-based medication called auranofin, also neutralized the enzyme. In an additional test in mice infected with S. mansoni, auranofin killed nearly two-thirds of the worms.
The researchers are exploring other compounds that might attack TGR with the aim to find one that is “less toxic than antimony and less expensive than gold,” Williams says.
S. mansoni lives in tropical waters and infects people through their skin. At present, the sole treatment for schistosomiasis is a drug called praziquantel, which proved to have no effect on TGR.