The search for a treatment for polycystic kidney disease (PKD), a disorder in which genetic mutations lead to the formation of cysts that impair kidney function, has led a Yale team to a Chinese plant-based medicine used for centuries to treat cancer, inflammation and other conditions. “The active ingredient has been known for 30 years, but nobody knew how it worked,” said Craig M. Crews, Ph.D., associate professor of chemistry, of molecular, cellular and developmental biology and of pharmacology. “We wanted to find out how this compound worked.”
Crews and colleagues found that the compound, known as triptolide, binds to a calcium channel encoded by the gene PKD2 and implicated in polycystic kidney disease. Furthermore, the gene that encodes that channel had been cloned by Stefan Somlo, M.D., FW ’91, the C.N.H. Long Professor of Medicine and professor of genetics. Triptolide is the active ingredient in the traditional Chinese medicine Lei Gong Teng, typically brewed as a tea.
In March, Crews and his team, in collaboration with Somlo, reported in the Proceedings of the National Academy of Sciences that triptolide reined in the rogue calcium channel in mice and thus appeared to mitigate the symptoms of PKD. “Our research shows that triptolide … markedly decreases cyst formation in a mouse model of this most common genetic lethal kidney disease,” Crews said.
PKD, Crews said, is the result of a gene mutation that confuses epithelial cells into thinking they’re at an earlier stage of development. As a result they continue to generate tubules that turn into fluid-filled cysts in the kidney. “They accumulate cysts to the point where after 40 or 50 years of life the kidneys are so full of cysts that they lose function,” he said. More than 12 million people worldwide suffer from the disease.
“The next step with triptolide is that we want to see if this may have an effect in humans,” Crews said.