Toxoplasmosis is a disease caused by Toxoplasma gondii, a protozoan. It is very common in cats, but also known in humans. This is the disease people worry about when they have children and cats in the same house. Don’t let your child eat cat poop! Pregnant women should avoid this disease, as there are especially bad outcomes for the offspring.The good news is this: A new drug currently in testing phase for treating malaria is very effictrive against T. gondii. This new drug, a form of triazine, goes by the memorable name JPC-2067-B.This finding is recently reported in PLoS Neglected Tropical Diseases (an On Line Open Access Journal).Here is the more or less comprehensible “author’s summary” (essentially, an “abstract” written in somewhat more understandable English) from the paper:
Toxoplasmosis is a neglected tropical disease, an emerging disease as well as a significant problem in developed countries causing a substantial health burden. Better medicines with less toxicity are greatly needed. Herein, we found that a novel triazine currently being advanced to clinical trials for malaria, JPC-2067-B, is highly effective against T. gondii. We demonstrate that JPC-2067-B inhibits T. gondii growth in culture (IC50 20 nM), inhibits the purified enzyme (IC50 6.5 nM), is more efficacious than pyrimethamine, and is cidal in vitro. JPC-2067-B administered parenterally and the orally administered pro-drug (JPC-2056) are also effective against T. gondii tachyzoites in vivo. A molecular model of T. gondii DHFR-TS complexed with JPC-2067-B was developed. We found that the three main parasite clonal types and isolates from South and Central America, the United States, Canada, China, and Sri Lanka have the same amino acid sequences preserving key binding sites for the triazine. Toxicology data are presented. JPC-2056/JPC-2067-B have potential to be more effective and less toxic treatments for toxoplasmosis than currently available medicines.
A triazine is an organic chemical with properties that make it useful in a number of different areas, from use in insecticides to use in dyes. “Cidal” means it can kill stuff. Like homicidal. To be administered parenterally means to be administered in a way other than by eating it, like into tissue or into the blood. In other words, administered in a way that does not subject the drug (or whatever) to the slings and arrows of the digestive system.Here’s a picture of the drug:This drug works by inhibiting the activity of the enzyme dihyrofolate reductase, which is apparently unique to this kind of portozoan (including the malaria parasite). There is a similar enzyme in humans, of course, we do all descend from a common ancestor, after all. But since we descended with modification, as discussed by Darwin, these enzymes are not exactly the same. So this new drug affects the version of the enzyme in the parasite but not (much) the version of the enzyme in humans.According to one of the study authors (McLeod), toxoplasma infection is
…probably the most common parasitic infection in the world, causing very significant disease in those who have immature immune systems or who are immune-compromised….An infected cat can excrete up to 20 million oocysts over two weeks…Even a single oocyst is infectious and they can remain infectious in water for up to six months and in warm moist soil for up to a year.
Mui, E.J., Schiehser, G.A., Milhous, W.K., Hsu, H., Roberts, C.W., Kirisits, M., Muench, S., Rice, D., Dubey, J.P., Fowble, J.W., Rathod, P.K., Queener, S.F., Liu, S.R., Jacobus, D.P., McLeod, R., Matlashewski, G. (2008). Novel Triazine JPC-2067-B Inhibits Toxoplasma gondii In Vitro and In Vivo. PLoS Neglected Tropical Diseases, 2(3), e190. DOI: 10.1371/journal.pntd.0000190