Praziquantel is the only drug available to treat schistosomiasis and has been used for decades in mass administration programs targeting entire populations. Treatment does not prevent later re-infections with larval worms if re-exposure occurs. The lack of alternatives to praziquantel is a concern because the parasites could develop resistance to the drug, resulting in no effective treatment for schistosomiasis.
Though safe and moderately effective, praziquantel’s molecular mechanism of action has not been characterized. An NIAID-supported research project is using planarian flatworms that develop two heads and an integrated nervous system under lab conditions to tease out how praziquantel interacts with flatworm nervous system protein receptors. Information gained could be used to develop new and improved treatments that disrupt similar protein receptors in schistosome flatworms.
Other projects are aimed at discovering compounds capable of inhibiting essential parasite enzymes. One research team is screening 100,000 compounds to identify any that inhibit a specific enzyme the parasite needs to establish infection in mammals. Additional screens will be used to separate out those compounds that are the most potent, specific and safe, and that could serve as the basis for new drug therapies.
Another effort is focused on a protein complex called a proteasome, which is used by several kinds of parasites, including the ones that cause malaria. In studies of malaria parasites, NIAID-supported researchers designed a potent and selective inhibitor of the malarial proteasome. They are now applying the technique to synthesizing proteasome inhibitors that act against S. mansoni parasites.