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Chinese Medicinal Compound Stops Formation Of Cysts In Polycystic Kidney Disease In Lab

Date:
April 30, 2007
Source:
Federation of American Societies for Experimental Biology
Summary:
Using a compound from a centuries-old Chinese traditional medicine, a Yale University researcher has been able to prevent the formation of kidney-destroying cysts in a mouse model of polycystic kidney disease.

Using a compound from a centuries-old Chinese traditional medicine, Yale University researcher Dr. Craig Crews has been able to prevent the formation of kidney-destroying cysts in a mouse model of polycystic kidney disease. This ability holds out hope for what would be the first treatment, other than kidney transplant or frequent dialysis, for one of the most lethal of all kidney diseases worldwide.

Triptolide is derived from a Chinese medicinal herb, named Lei Gong Teng, which has been used in traditional medicine to treat cancer, inflammation, and auto-immune diseases and, more recently, also has been tested in Phase I clinical trials as an anti-tumor agent.

This study, with mice bred to have a disease like human polycystic kidney disease, used triptolide with a less toxic concentration than that used in cancer chemotherapy trials. At that level, the compound marked reduced cyst formation in the mice compared to genetically similar mice not taking the compound.

During normal kidney development, cells lining the kidney tubules continue growing and dividing until they receive a signal that the tubule is fully formed. The switch that turns on that signal consists of the growth regulatory proteins PKD1 and PKD2, located on hair-like cilia in the lining of the developing tubules. When urine begins flowing through the tubules, the flow bends the cilia that sets off the signal that no more growth is needed.

In people who have a mutation in one of these growth regulatory proteins, however, the message to stop growing never gets delivered, even when urine is flowing and the cilia are bending. It is as if the phone is ringing but the cell can't hear it. So, never sensing a signal to stop, the cells lining the fully-formed kidney tubules keep right on subdividing and growing. The result of this hyperproliferative, unregulated growth: uncontrolled growth of cells lining the tubules and the formation of large cysts in the kidneys.

The vast majority - 85 percent - of patients with polycystic kidney disease have a gene causing PKD1 to be missing or to function poorly. Because most patients inherit only one abnormal gene and one functional gene, the body is usually able to compensate for the faulty gene and the person retains kidney function during the 20s and 30s. But through random mutagenesis, the remaining good copy of PKD1 is lost in some cells, which then switch to the hyperproliferative state. As the person's kidney begins to develop these cysts, the kidney begins to swell, and the person moves to either dialysis or transplant in order to survive.

That means a treatment that slows down the development of cysts does not have to stop their production completely to be effective, says Dr. Crews.

"If we were able to slow the rate of cyst formation by even 10 percent a year, compounded annually, patients would not die from this disease. A relatively small effect would have an enormous clinical benefit," says Dr. Crews.

Dr. Crews described the functioning of the compound at Experimental Biology 2007 in Washington, DC. His presentation on April 29 is part of the scientific program of the American Society for Biochemistry and Molecular Biology.

One of Dr. Crews' collaborators on this study, and one of the co-authors of this Experimental Biology presentation (and a related publication, earlier this month, in Proceedings of the National Academy of Science about the effect of the compound), is Dr. Stefan Somlo, chief of nephrology at Yale, who discovered the PDK2 gene. Other co-authors of the Experimental Biology presentation are Stephanie J. Leuenroth, Dayne Okuhara, Joseph D. Shotwell, Glen S. Markowitz, and Zhiheng Yu.

The researchers are continuing this research in different mouse models of polycystic kidney disease and hope to see the compound proceed to clinical trials in humans.


Story Source:

The above story is based on materials provided by Federation of American Societies for Experimental Biology. Note: Materials may be edited for content and length.


Cite This Page:

Federation of American Societies for Experimental Biology. "Chinese Medicinal Compound Stops Formation Of Cysts In Polycystic Kidney Disease In Lab." ScienceDaily. ScienceDaily, 30 April 2007. <www.sciencedaily.com/releases/2007/04/070429154947.htm>.
Federation of American Societies for Experimental Biology. (2007, April 30). Chinese Medicinal Compound Stops Formation Of Cysts In Polycystic Kidney Disease In Lab. ScienceDaily. Retrieved September 21, 2014 from www.sciencedaily.com/releases/2007/04/070429154947.htm
Federation of American Societies for Experimental Biology. "Chinese Medicinal Compound Stops Formation Of Cysts In Polycystic Kidney Disease In Lab." ScienceDaily. www.sciencedaily.com/releases/2007/04/070429154947.htm (accessed September 21, 2014).

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