Figure 1: A light micrograph of the larva of the parasitic flatworm that causes the disease schistosomiasis in people. A RIKEN researcher has discovered the basis of a new drug for treating the disease caused by the parasite. © STEVE GSCHMEISSNER/SCIENCE PHOTO LIBRARY
A series of compounds that deprive iron essential for a parasitic worm could provide effective new agents for blocking parasite growth, a RIKEN researcher has found1. This finding could give a much-needed new strategy for fighting the parasite.
Parasitic flatworms of the genus Schistosoma cause the neglected tropical disease schistosomiasis, which leads to acute symptoms such as diarrhea, fever and bloody urine. Chronic infections can damage the liver, intestine, bladder and kidney. Globally, there are estimated to be about 250 million sufferers, of which about half are children of school age.
Praziquantel was developed as a drug for treating schistosomiasis about five decades ago, but there are concerns that the parasites could develop resistance. It is thus important to develop new drugs that employ different strategies for combating schistosomiasis. Since praziquantel specifically attacks adult worms, it is highly desirable to develop new alternative drugs that can kill their larval forms, schistosomula and cercariae (Fig. 1).
That is what Akira Wada of the RIKEN Center for Integrative Medical Sciences wanted to do. "To help improve the current situation with schistosomiasis, we aimed to discover untapped compounds that have the potential to be new antischistosomal drugs," says Wada.
His group had recently shown that snatching iron from malaria and amebic parasites using metal-binding compounds curtailed their growth. He wondered if the same strategy could be effective against Schistosoma species.
Now, Wada and his collaborators have shown that such compounds are able to kill schistosomula in mice more efficiently than the first-line drug for the disease, making them a promising basis for new drugs.
"Our results suggest that the unique approach for containing the iron source essential for Schistosoma parasites could provide valuable insights for developing a next-generation antischistosomal drug," says Wada.
As an added bonus, one of the compounds also interfered with the egg-laying behavior of female adult worms, significantly suppressing the production of parasite eggs in mice. This shows that the parasite needs iron in both the larval and egg-laying stages.
The strategy could be effective against other parasites, Wada believes. "In general, pathogenic parasites have inherent systems for acquiring iron needed to promote their growth, differentiation and maturation," he says.
Wada is keen to uncover new potential drugs for other neglected tropical diseases, adding: "I would like to continue to work on drug discovery research for neglected tropical diseases for which drug treatments have not yet been established."
