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Itaconate compound a potential Tx for psoriasis

Dimethyl itaconate, a modified form of an inflammation-regulating compound derived from inflammatory cells, appears to reduce psoriasis symptoms in a mouse model by reducing levels of the protein IκBζ in the interleukin(IL)-17 pathway.

These findings come from a paper published in Nature (Apr. 18, 2018, online ahead of print).

The authors had previously shown that inflammatory cells that detect the presence of bacteria produce a compound called itaconate that dampens inflammation.

Prior genetic studies of people with psoriasis have also found a link between variations in the gene for IκBζ and a higher risk of developing psoriasis, the authors note.

In an effort to understand how and why this dampening occurs, the researchers induced psoriasis-like symptoms in the ears of mice and injected the animals with either dimethyl itaconate or a placebo daily, for one week. At the end of the test period, mice in the placebo group still had red, swollen ears, while those in the active group had normal-looking ears.

“We are taking advantage of the body’s own anti-inflammatory power and showing that it can help in real situations when your own immune system is hurting you,” said senior author Maxim Artyomov, PhD, an assistant professor of pathology and immunology at the Washington University School of Medicine in St. Louis, in a press release.

The IL-17 pathway plays a role in many autoimmune diseases, so the research team suspects dimethyl itaconate may be helpful for treating a number of conditions. Dr. Artyomov and his colleagues have begun studying if itaconate compounds can reduce the signs of multiple sclerosis in mice.

“Since we first linked itaconate to inflammatory cell activation in 2016, it has been surprising us,” Artyomov said. “Everyone thought that if it is produced by inflammatory cells it should fight infection, but no—it’s anti-inflammatory. Now we know that itaconate compounds can help with autoimmune diseases, specifically in psoriasis and potentially in multiple sclerosis. This small molecule is turning out to be really powerful.”

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