Will new approach cure Chagas disease?

From Chicago, at the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy

By disabling the parasite that causes Chagas disease, a simple drug might offer a way to stop this deadly condition that affects 18 million people in Latin America.

Chagas disease, which can damage the heart, results from infection by a parasite called Trypanosoma cruzi that’s spread by insects. To thwart this protozoan, researchers have targeted squalene synthase, an enzyme that T. cruzi uses to make fat components called sterols. The parasite needs sterols to survive.

Chemist Julio A. Urbina of the Venezuelan Institute of Scientific Research in Caracas and his colleagues used the chemical BPQ–for 3-(biphenyl-4-yl)-quinuclidine–which is known to inhibit squalene synthase. When they combined BPQ with T. cruzi in a test tube, the chemical halted the parasite’s production of squalene synthase, killed the parasite, and yet did not harm monkey cells in the test tube, Urbina reports.

“Nobody had thought of blocking [squalene synthase] as an antiparasitic approach,” Urbina says. “We show that death of the parasite is absolutely associated with disappearance of its specific sterols.” T. cruzi‘s main sterol is chemically similar to sterols in plants, so it can’t use parts of fat, such as cholesterol, from people. When its squalene synthase is disabled, Urbina says, “the parasite has no way to compensate.”

T. cruzi grows in heart and nerve cells, causing chronic inflammation and eventually heart damage. Roughly 4 million people have such late-stage disease, Urbina estimates.

“This is a very serious, insidious disease,” he says. Urbina plans to experiment with BPQ in animals and to test other chemical inhibitors of squalene synthase. Says Urbina: “The first priority will be to stop infections before they get to the heart.”

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