Small Molecule Drug Could Prevent Kidney Fibrosis

ETC159, currently in phase I trials for colorectal, ovarian and pancreatic cancers, could also be used to treat liver fibrosis.

AsianScientist (Mar. 30, 2016) – Researchers from Duke-NUS Medical School (Duke-NUS) in Singapore have shown that drugs that target Wnt secretion may reduce kidney fibrosis, a precursor to end stage kidney disease. Their findings have been published in Kidney International.

Patients with chronic kidney disease often develop kidney fibrosis or scarring, which can cause the disease to progressively worsen. Despite an intense focus of research in this area, no specific therapies are currently available to treat or reverse fibrosis in human chronic kidney disease.

An effective drug against fibrosis would allow patients to lead more productive and independent lives. It would also have a positive impact on the healthcare system. As such, finding alternative treatments for kidney fibrosis before it reaches this advanced stage is necessary.

A team led by Assistant Professor Babita Madan and Professor David Virshup from Duke-NUS, and Associate Professor Steven D. Crowley from Duke University, used a mouse model of kidney fibrosis to explore whether Wnt secretion inhibitors can be used to treat fibrosis. Wnt secretion inhibitors are presently being tested for the treatment of certain cancers.

To induce fibrosis in the mice, the researchers blocked the ureter connecting the kidney to the bladder, causing the affected kidney to become damaged and scarred. The team demonstrated that inhibiting Wnt secretion interrupted the dangerous build-up of scar tissue in the kidney.

These findings suggest a novel therapeutic approach to protect the kidney from scarring and provide a compelling rationale to test the use of Wnt secretion inhibitors for the treatment of kidney fibrosis and other progressive scarring disorders.

“This is the first study to demonstrate that a Wnt secretion inhibitor can be useful for preventing renal fibrosis,” explained first author Madan. “There could be potential long-term therapeutic treatments that could arise from this new knowledge, which can be explored for the treatment of additional fibrotic disorders including kidney disease.”

Virshup, director of the Cancer and Stem Cell Biology Program at Duke-NUS and Madan, in collaboration with A*STAR’s Experimental Therapeutics Center, have developed a novel Wnt secretion inhibitor, ETC-159. ETC-159 is presently in a phase I clinical trial to target different cancers. Based on the findings of this study, it may be possible to test whether ETC-159 and other Wnt secretion inhibitors can be used to treat diseases other than cancer.


The article can be found at: Madan et al. (2016) Experimental Inhibition of Porcupine-Mediated Wnt O-Acylation Attenuates Kidney Fibrosis.

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Source: Duke-NUS Medical School.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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