Treating infected mice with ergotamine eliminated the parasites and reduced the organ damage caused by the infection. A drug called ergotamine, which is currently used to treat migraines, strongly interacted with the protein. screened thousands of existing chemicals for interactions with a protein that is known to control how the worms move. One possible approach would be to develop drugs that interfere with the worm’s ability to move.Ĭhan et al. This means there is an urgent need to develop new therapies. However, the drug has unpleasant side effects, cannot cure all infected individuals, and there is a concern that worms may develop resistance to its effects. This means there has not been adequate investment into developing new treatments or cures.Ī drug called praziquantel is currently the only treatment for schistosomiasis. Despite its significant health and economic impact, schistosomiasis is still considered a ‘neglected’ tropical disease. Long-term infections can damage organs, and children who are affected may suffer delayed growth and learning difficulties. More than 200 million people worldwide are infected with parasitic worms that cause the disease schistosomiasis. The unique ability of ergotamine to engage both host and parasite GPCRs evidences a future strategy for anthelmintic drug design that coalesces deleterious antiparasitic activity with beneficial host effects. In vivo, ergotamine decreased mortality, parasite load and intestinal egg counts but also uniquely reduced organ pathology through engagement of host GPCRs that repressed hepatic stellate cell activation, inflammatory damage and fibrosis. A target-based screen of a Schistosoma serotoninergic G protein coupled receptor yielded the potent agonist, ergotamine, which disrupted worm movement. This principle is evidenced through a screen for drugs to treat schistosomiasis, a parasitic flatworm disease that impacts over 230 million people. Here, we show that agents with a broad polypharmacology, often considered ‘dirtier’ drugs, can have unique efficacy if they combine deleterious effects on the parasite with beneficial actions in the host. Conventional approaches for antiparasitic drug discovery center upon discovering selective agents that adversely impact parasites with minimal host side effects.
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