Spanish National Cancer Research Center Offers Potential Genetic Treatment Options for Psoriatic Arthritis

New genetic treatment options are being explored using mice models of psoriasis in two studies, including inhibiting genes and proteins.

Scientists have created 2 different potential treatments for psoriatic arthritis based on mice models modified 10 years ago.

The first study, published in Immunity by researchers at the Spanish National Cancer Research Center (CNIO), details how the symptoms of psoriasis disappear after deleting a protein called S100A9. Scientists compared skin affected by psoriasis to healthy skin from the same donor from 19 patients. The researchers identified 1217 proteins and found 214 differences between the samples of healthy and affected skin. The protein complex S100A8-S100A9 was much more abundant in psoriasis.

The researchers then generated a mouse prone to psoriasis but deleted the protein S100A9. The symptoms of psoriasis then disappeared in the mouse model. Investigators now hope to find other targets the protein S100A8-S100A9 acts on. A drug blocking S100A9 is already on the market, but the authors say that this does not mean it will be approved.

According to the second study, published in Science Translational Medicine, inhibiting non-coding a micro-RNA called miR-21 eradicates the symptoms of psoriasis. The micro-RNAs, whose roles are not entirely understood, are small fragments of nucleic acid that are not translated into protein and regulate the expression of other genes.

Researchers inhibited miR-21, which is more abundant in psoriatic skin than healthy skin, in mouse models of psoriasis. They observed the disappearance of symptoms without any side effects. They repeated a similar process with human samples, grafting human skin onto live mice. This allowed researchers to study reactions with human tissue without treating a human patient. The mice’s grafted skin was treated with the compound the blocks miR-21, which proved effective again.

Both studies have identified some of the key alterations that can be made and identified potential new targets.

“Hundreds of increased or decreased genes have been described for psoriasis, but only a few of them—dozens—are supposed to be able to cause the disease,” the authors said. “We have described two new genes/proteins that are known to show increased levels in psoriasis, and have now shown that they play a causal role in the disease.”