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Researchers find ways to reduce side effects in the treatment of damaging protein plaques

COLUMBIA, Mo. When protein plaque builds up in the blood, it can result in serious diseases such as heart disease and Alzheimer's. Cyclooxygenase (COX) inhibitors, a class of drugs under investigation for the treatment of one cause of plaque build-up, also exhibit negative side effects.

Researchers in the International Institute of Nano and Molecular Medicine at the University of Missouri-Columbia are studying the possible use of carboranes, which are clusters of boron and carbon atoms, to prevent such side effects. These boron-rich clusters are substituted for carbon-based benzene rings commonly found in pharmaceuticals of all types, including COX inhibitors, which give unwanted side effects.

COX activity is seen in common nonsteroidal anti-inflammatory drugs like aspirin and ibuprofen. However, prolonged use of COX inhibitors can result in a variety of negative side effects, such as possible digestive and liver problems. Some COX inhibitors have recently been pulled from the market due to an increased risk of heart complications.

The protein transythyretin acts as a shuttle to transport thyroxine, a hormone, throughout the body. As the least important of the three blood proteins that carry thyroxine, transthyretin also has a tendency to fall apart and form tough, insoluble plaques, sometimes causing injury to delicate tissues. Certain people are genetically more likely to have the proteins fall apart, increasing the risks. Investigators have found that in laboratory experiments, certain COX inhibitors help stabilize the structure of transthyretin protein, and therefore prevent harmful plaque formation.

"The successful identification of carborane-containing surrogates for known COX inhibitors based exclusively on carbon chemistry greatly strengthens the concept that carboranes can be substituted for carbon-rich portions of known pharmaceuticals, and in so doing, improve its efficacy and safety," said M. Frederick Hawthorn
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Contact: Katherine Kostiuk
KostiukK@missouri.edu
573-882-3346
University of Missouri-Columbia
24-Apr-2007


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