Radiation-caused Fibrosis in Mice Successfully Treated by Anti-scarring Paste

In a new study, researchers applied a novel anti-scarring paste to animal models with radiation-induced fibrosis and observed a healing and preventive effect. Such results indicate a promising therapeutic effect of A2A receptor blocker-derived drugs, such as this paste, for conditions like scleroderma and interstitial pulmonary fibrosis. The research paper, titled “Adenosine A2A receptor plays an important role in radiation-induced dermal injury,” was published in The Journal of the Federation of American Societies for Experimental Biology.

The research team, led by senior study author and rheumatologist Dr. Bruce Cronstein, director of NYU Langone’s Clinical and Translational Science Institute, had previously demonstrated that occupancy of the A2A receptor stimulates the production of collagen, the main structural protein in connective tissues. Consequently, researchers theorized that deletion or blockage of this receptor would halt fibrosis, a damaging process in which excessive connective tissue is wrongly created, leading to deterioration and/or malfunction of tissues and organs.

To test their hypothesis, researchers irradiated normal and A2A receptor-deficient mice to develop a fibrosis condition called radiation dermatitis, a side effect of radiation therapy experienced by many cancer patients. Half of the irradiated mice were treated with an antiscarring paste based on a A2A receptor blocker, while the other half received a placebo.

The results showed that, after a month, the placebo group exhibited a nearly two-fold increase of collagen, skin thickness and fibrosis, while mice treated with the anti-fibrotic paste experienced only a 10% increase in collagen-derived skin thickness. Mice lacking the A2A receptor had no skin response to the radiation.

Dr. Cronstein said of the results in a press release, “Our latest study is the first to demonstrate that blocking or deleting the A2A receptor can be useful in reducing radiation-induced scarring in skin. The study also suggests that adenosine A2A receptor antagonists may have broad applications as drug therapies for preventing fibrosis and scarring, not just in the liver but also in the skin.”

The team’s future research plans will focus on the A2A receptor’s role in fibrosis development. The researchers believe that if experiments in animal models and humans are successful, this paste or a similar drug could become an effective therapy for fibrosis prevention, not only in cancer patients undergoing radiation therapy but also in diseases where changes in collagen structure occur, like scleroderma and interstitial pulmonary fibrosis. The research of novel therapies targeting fibrosis is essential, since available treatments are scarce and not very effective.