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.
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.
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,
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Federation of American Societies for Experimental Biology
29-Apr-2007