Compound mimicking gene deletion stops tissue scarring in mice

By targeting a family of proteins on the surface of certain cells, scientists have been able to halt and reverse tissue scarring in the liver, kidneys and lungs of mice.

The finding, by investigators at the University of California, San Francisco, could have implications for treating the same kind of scarring in humans--called fibrosis, which is a major contributor to nearly half of all deaths in developed nations. Currently, there is no way to treat tissue scarring from chronic diseases. The study was published Nov. 10 in Nature Medicine.

"Scarring is a critical component of organ dysfunction in most chronic diseases--kidney failure, liver failure, lung failure, heart failure," said Dr. Dean Sheppard, UCSF professor of medicine and senior author of the new study, in a statement. "But there's no effective therapy for tissue scarring that's approved by the FDA."

An international team of scientists, led by first author Dr. Neil Henderson of the University of Edinburgh, developed a genetic technique to selectively turn off a 5-member family of receptors known as alpha V integrins in the collagen-producing fibroblast cells of mice. The expression of these cells helps induce the excessive scarring seen in fibrosis. In normal mice--those lacking the alpha V integrins--the genetic deletion had little effect. In mice with alpha integrins, the method guarded against fibrosis of the lungs and kidney. The same protective effect was not observed when scientists tried turning off individual members of the alpha V integrin family, suggesting that the whole family may be a viable target for treating fibrosis.

Using these findings, members of the team based at St. Louis University in Missouri designed a drug called CWHM 12 that works by suppressing all 5 alpha V integrins. The compound not only worked the same way to prevent fibrosis as the genetic deletion method, it also prevent the progression of existing fibrosis in the liver and lungs and reversed some of the damage caused by fibrosis to those organs.

Sheppard said delivering CWHM 12 or a similar small molecule directly into the lungs as an inhalant might offer a way to treat lung fibrosis. 

- here's the press release
- see the study abstract

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