Key result
SB-431542 treatment significantly reduced mortality to 56% compared to 86% in untreated mice at 22 days postinfection, and prevented heart damage in a mouse model of acute Chagas' disease.
Why the study?
Does SB-431542 reduce mortality and prevent heart damage in a mouse model of acute Chagas' disease?
Does SB-431542 reduce mortality and prevent heart damage in a mouse model of acute Chagas' disease?
Absolute Event Rate: 56% vs 86%
p-value: p=<0.05
Inhibition of TGF-beta signaling with SB-431542 reduces mortality and prevents cardiac conduction abnormalities in a preclinical mouse model of acute Chagas' disease.
May support TGF-β inhibition in acute Chagas' disease; leaves open human translation and safety.
Chagas' disease induced by Trypanosoma cruzi infection is an important cause of mortality and morbidity affecting the cardiovascular system for which presently available therapies are largely inadequate. We previously reported that transforming growth factor beta (TGF-beta) is implicated in several regulatory aspects of T. cruzi invasion and growth and in host tissue fibrosis. This prompted us to evaluate the therapeutic action of an inhibitor of TGF-beta signaling (SB-431542) administered during the acute phase of experimental Chagas' disease. Male Swiss mice were infected intraperitoneally with 10(4) trypomastigotes of T. cruzi (Y strain) and evaluated clinically for the following 30 days. SB-431542 treatment significantly reduced mortality and decreased parasitemia. Electrocardiography showed that SB-431542 treatment was effective in protecting the cardiac conduction system. By 14 day postinfection, enzymatic biomarkers of tissue damage indicated that muscle injury was decreased by SB-431542 treatment, with significantly lower blood levels of aspartate aminotransferase and creatine kinase. In conclusion, inhibition of TGF-beta signaling in vivo appears to potently decrease T. cruzi infection and to prevent heart damage in a preclinical mouse model. This suggests that this class of molecules may represent a new therapeutic agent for acute and chronic Chagas' disease that warrants further clinical exploration.
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Waghabi et al. (2009) studied Acute Chagas' disease. SB-431542 vs. Vehicle (DMSO) was evaluated on Mortality at 22 days postinfection (p=<0.05). SB-431542 treatment significantly reduced mortality to 56% compared to 86% in untreated mice at 22 days postinfection, and prevented heart damage in a mouse model of acute Chagas' disease.
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