An anti-leukemia drug: potential for psoriasis

The drug dasatinibapproved to treat certain types of leukemia, has been shown to be effective in blocking an immune system pathway and reducing inflammation associated with psoriasis in an experiment with mice led by a team from the Severo Ochoa Molecular Biology Center of the Higher Council for Scientific Research and the Autonomous University of Madrid (CBM-CSIC-UAM).

Psoriasis is a chronic inflammatory disease that affects millions of people around the world and It causes redness, peeling and thickening of the skin. It originates when the immune system is activated excessively and produces substances that irritate the skin.

This study, published in Journal of Allergy and Clinical Immunologyshows that dasatinib can stop this process, which involves different molecules that immune cells use to communicate with each other.

Among these molecules, cytokines stand out.which act as chemical signals. One of those signs, called interleukin 23 (IL-23), activates certain immune cells and prompts them to produce another inflammatory molecule called IL-17which contributes to triggering skin inflammation.

The key to stopping inflammation is to act against the relationship between IL-23 and IL-17for which in recent years treatments have been developed that have managed to improve the control of the disease. However, little is still known about how the IL-23 signal is transmitted within immune cells, which is what the researchers of this work wanted to focus on.

Drug repositioning

Experts evaluated drugs already approved for other diseases in order to identify new therapeutic uses. This strategy, known as drug repositioning, allows for faster progress, since the safety and basic functioning of the drugs is already known.

The team analyzed a collection of drugs authorized by regulatory agenciesobserving that some of them interfered with the inflammatory pathway activated by the IL-23 molecule. Among them, dasatinib stood out for its ability to block IL-23-induced IL-17 production in immune system cells.

After that, they verified that the inhibitory effect occurred in the same way in an experimental model of skin inflammation similar to psoriasis. As they verified, The treatment reduced skin thickening, the accumulation of immune cells in the inflamed area, and the presence of IL-17-producing cells.

These effects were observed both when the drug was administered through the blood, reaching the entire body, and when it was applied directly to the skin. This finding suggests that the medication could be used in the form of creams, avoiding exposure to the rest of the body.

Inflammation transmission mechanism

The study also identifies the mechanism of transmission of the inflammatory signal within cells. According to him, IL-23 activates a chain of proteins that function as molecular switches and end up activating cellular complexes called mTORwhich regulate the activity and metabolism of cells and are important in the inflammation process.

A specific protein called Blk participates in this process.which acts as an intermediary between the IL-23 signal and the activation of the inflammatory response. Until now, it was not known that Blk acted as a mediator in the inflammatory cascade of psoriasis, so this finding opens a new therapeutic target for future treatments.

Although more studies will be necessary to evaluate the safety and effectiveness of the findings, the work opens new avenues for the development of therapies against chronic inflammatory diseases.