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Penn receives $1.2 million grant for further development of Compstatin, a drug to halt an overzealous immune system

(Philadelphia, PA) In some ways, the bodys first line of defense can also be its worst enemy. The complement system is a series of biochemical reactions that activate in response to foreign molecules and is an important part of the immune system. Unfortunately, when it is activated at the wrong time, complement is also responsible for organ transplant rejection and a long list of diseases.

Researchers at the University of Pennsylvania Medical Center have found a way to control complement with Compstatin, a small molecule that blocks the reactions involved in a complement response. The National Institute for General Medical Sciences (NIGMS) has awarded John D. Lambris, PhD, a professor in the Department of Pathology & Laboratory Medicine, a $1.2 million grant to continue the development of Compstatin into an effective drug.

"Among the compounds we have studied, I believe Compstatin holds real promise,"said Lambris. "Until Compstatin, most complement inhibitors were either only marginally effective or actually toxic to humans."

Part of the reason it has been so difficult to control complement is because of the complex nature of the human immune system. Complement proteins serve as a passive alarm system, watching for pathogens that may enter the blood system. When a complement protein finds something it does not recognize, it attaches itself to the invader, summoning the full wrath of the immune system, which attempts to destroy the invader. Complement is not a simple sequence of reactions either, but a series of interlocking cascades, or chain reactions, of biochemical events involving at least 30 proteins.

"Fortunately, there is a point where all the protein cascades intersect,"said Lambris. "We figured that if we can stop the cascade at this point, we can halt the reaction regardless of what pathway started it.

Lambris and his colleagues focused on one particular complement protein, an enormous molecule called C3. They created billions
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Contact: Greg Lester
lesterg@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
11-Mar-2001


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