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

PHILADELPHIA The interaction of the drug compstatin with two ancient, co-evolved human systems points to new ways for reducing clotting during dialysis for end-stage kidney disease and multiple organ failure due to sepsis, a dangerous whole-body inflammatory response to infection.

"It has been suspected, but not demonstrated in cells and animals, until now, that these two systems are able to interact," says study author John D. Lambris, PhD, the Dr. Ralph and Sallie Weaver Professor of Research Medicine at the University of Pennsylvania School of Medicine. "Our basic research on these two interacting human systems is helping us to come up with new ways to stop clotting problems."

One system, called complement, an evolutionarily old arm of the immune system, comprises a network of proteins that "complement" the work of antibodies in destroying foreign invaders. The system serves as a rapid defense mechanism in most species from primitive sponges to humans.

The second system, coagulation, or blood-clotting, is also evolutionarily old and co-evolved with the complement system.

Penn researchers, along with an international team of collaborators, describe that inhibition of the complement system using compstatin helps to stop clotting problems during dialysis and in cases of sepsis, according to two recent articles published online in Blood.

Compstatin is a small molecule designed to specifically and maximally inhibit the complement reaction to invading substances by attaching to a complement molecule called C3.

Reaction to Dialysis Materials

Complement activation is often triggered by the tubing and filters used during dialysis itself, causing problems with blood clotting. However, the mechanism by which long-term dialysis causes clotting has not been clear. In the U.S. more than 500,000 receive treatment for end-stage renal disease annually.

In recent years, the adverse effects of
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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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