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Team Finds Compounds that Prevent Nerve Damage

By R&D Editors | September 28, 2008

Duke University Medical Center scientists have made a significant finding that could lead to better drugs for several degenerative diseases including Huntington’s disease and Alzheimer’s disease. Compounds that block the activity of a specific enzyme prevented brain injury and greatly improved survival in fruit flies that had the same disease process found in Huntington’s disease.

“We were able to prevent Huntington’s disease-like illness in mutant fruit flies by giving them orally active transglutaminase inhibitors,” said Charles S. Greenberg, M.D., a Professor of Medicine and Pathology at Duke University Medical Center and senior author of the paper. The drug blocks the action of tissue transglutaminase (TGM2),which may damage cells by forming strong bonds between proteins. Such bonding is beneficial for blood clotting which happens outside of cells, but if this type of bonding occurs inside cells, it can be harmful, Greenberg said.

While these compounds were promising in the animal system, they are several years away from entering any human trials.

For the study, 2,000 compounds were screened. Only two groups of drugs were found to be effective TGM2 inhibitors. Some of the most potent TGM2 inhibitors were given to the fruit flies along with their food.

The most effective compound was a kinase inhibitor, a drug that had been developed several years ago for another purpose. The other beneficial compounds fell into a category of drugs that attack a sulfhydryl group in a protein.

The next step is to use the effective compounds as the backbone for developing even more effective drugs. The scientists plan to test whether the TGM2 inhibitors they identified would prevent the fibrous tissue process that causes chronic renal, vascular, and lung disease.

Release date: September 23, 2008
Source: Duke University Medical Center

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