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New drug shows promise for kidney disease
Date:8/3/2012

bs. "He happens to be the chief scientist at a biopharmaceutical company that may have the technology to make a better drug that could work for PKD patients."

In an earlier study by Weimbs and other researchers, a signaling protein called mTOR was found to drive cyst growth in polycystic kidney disease. Weimbs then found that rapamycin inhibited the growth of cysts, which caused great excitement in the field. However, when the drug was used in large clinical trials in Europe, the results were disappointing. The dose at which this drug could safely be used proved too low to affect kidney cysts.

But Leamon and Weimbs found a way around this problem. Endocyte Inc., Leamon's firm, specializes in linking or "conjugating" small molecules to target diseased cells, primarily cancer cells. Leamon explained that many cancers have a high affinity for folate, and that by linking folate to certain cancer drugs, his company has been successful in targeting cancer cells with these drugs. Leamon and Weimbs wondered if the same strategy could be used in treating the kidney cysts found in PKD. They examined both mouse and human PKD cysts and found that they did, in fact, express folate receptors.

Endocyte chemically synthesized a new version of rapamycin called folate-conjugated rapamycin (FC-rapa). Weimbs' laboratory tested this new drug and found that it was still highly effective in preventing kidney cyst growth in mice with PKD, but that it had fewer systemic side effects compared to regular rapamycin. The results suggest that FC-rapa could also be effective in human PKD patients without causing the significant unwanted side effects of regular rapamycin.

"FC-rapa is a fascinating drug because it combines an extremely specific drug with a delivery approach that targets it to a specific organ, the kidney," said Weimbs. "Rapamycin is already one of the most specific drugs on a molecular level, as it only affects the mTOR protein. The problem is th
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Contact: Gail Gallessich
gail.g@ia.ucsb.edu
805-893-7220
University of California - Santa Barbara
Source:Eurekalert  

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