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Action of modern drug demonstrates how 2 ancient human systems interact
Date:6/16/2010

dialysis have become a serious health and economic problem nationwide: The number of patients with end-stage renal disease has been steadily increasing in the U.S. over the past few decades, at a rate of approximately 9 percent per year, the highest increase in any developed country.

To solve this problem, Lambris reasoned that if the complement system was involved in triggering blood clotting, then inhibition of complement by compstatin binding to C3 would also stop the clotting. "We found that materials used in dialysis trigger the complement system and that the generation of certain complement molecules results in the expression of active tissue factor, a key initiator of clotting," said Lambris. The Penn group found that compstatin blocks the activation of two complement molecules, C3 and C5.

These findings suggest that compstatin, or other drugs that target the complement system, might be therapeutic agents to prevent clotting in patients with renal failure who are maintained on long-term dialysis.

Staying Sepsis

During severe sepsis, which accounts for about 210,000 deaths annually in the US, the complement system is part of the primary response to an invading pathogen. However, both the complement and the coagulation systems can work overtime during sepsis, leading to multiple organ failure and death.

In a baboon model of severe sepsis caused by a sub-lethal dose of E. coli, Lambris and colleagues found that treating the animals with compstatin during the acute or secondary phase of sepsis reduced both blood and tissue markers of complement activation and blood coagulation.

"Similar to the dialysis study, this shows that there is an interplay between the complement and coagulation systems," said Lambris.

Blocking the interplay between the two systems by compstatin, or a similar drug, may become a therapeutic strategy to prevent the devastating effects of sepsis.

"We are investigati
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert

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