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Scientists discover that widely available drug also helps fight kidney disease

ontrols an important regulatory protein called mTOR. A defect in polycystin-1 leads to over-activation of mTOR. This, in turn, causes excess growth and proliferation of kidney cells, which results in the formation of thousands of cysts that eventually destroy the kidney.

Fortunately, a highly effective inhibitor of mTOR is well known. This drug, rapamycin, was originally discovered in the 1970s in soil from Easter Island. It is used for immunosuppression in kidney transplant patients to prevent rejection of the new kidney.

Weimbs and his colleagues wondered about treating kidney patients with rapamycin. Most kidney transplant patients keep their diseased kidneys in place and the transplanted kidney is an additional, third kidney. So his colleagues, David A. Goldfarb and Andrew Novick, at the Cleveland Clinic in Ohio, suggested studying transplant patients who had received rapamycin to help their bodies accept the new kidney.

The research team identified a group of four rapamycin-treated patients and found that their polycystic kidneys shrank in size by 25% over two years. The polycystic kidneys in a control group showed no change.

"Even though we only had a very small number of patients, this result is highly encouraging because it points in the right direction," said Weimbs.

It shows, for the first time, a connection between polycystin-1 and mTOR, and strongly suggests that rapamycin may be a promising drug for treating PKD, explained Weimbs. "The fact that rapamycin is already clinically approved for other uses will facilitate future clinical trials of the drug."

Co-authors on the paper with Weimbs are: Jonathan M. Shillingford and Seng Hui Low in the Department of Molecular and Cellular Biology at UCSB; Claire H. Larson at the Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland Ohio; Ryan Hedgepeth, Andrew C. Novick, and David A. Goldfarb at the Glickman Urological Institute, Cleveland
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Source:University of California - Santa Barbara


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