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New hope for Chagas disease treatment

Chagas disease, which is transmitted to humans by a blood-sucking insect known as an Assassin bug, is the most devastating parasitic infection in Central and South America and Mexico. The protozoan parasite that causes the disease, Trypanosoma cruzi, infects 16 to 18 million people, causing severe chronic illness and tens of thousands of deaths per year.

Until now, there has been no effective treatment for the long-term, chronic form of Chagas disease, which kills up to one-third of those infected, usually by heart failure. However, two Howard Hughes Medical Institute (HHMI) international research scholars have now found that in mice, a compound called TAK-187 is significantly more effective than the current standard of care the drug benznidazole in preventing T. cruzi-induced cardiac damage. Julio Urbina from theVenezuelan Institute for Scientific Research and Miguel Angel Basombro from the National University of Salta and colleagues report their findings in the April issue of the journal Antimicrobial Agents and Chemotherapy.

Benznidazole, a drug used to treat acute, recent Chagas infections, often has toxic side effects and does not work once the disease has entered its chronic phase. As an alternative, Urbina, Basombro, and colleagues tested TAK-187, a compound that prevents T.cruzi from producing a member of the steroid family called ergosterol, which is essential to the parasite's life cycle. The compound is currently in development as a systemic antifungal agent, but the results of the current study suggest that drugs of this type, which inhibit ergosterol synthesis, could be a "superior alternative to currently available therapy in the management of chronic Chagas disease," Urbina and Basombro write in their report.

The scientists infected a group of mice with T.cruzi, then treated those mice with either TAK-187, benznidazole, or nothing at all. While both drugs completely eliminated T.cruzi from the blood of infected animal
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Contact: Jennifer Donovan
donovanj@hhmi.org
240-401-5783
Howard Hughes Medical Institute
31-Mar-2005


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