Rheumatoid arthritis, tests on a new therapy with fewer side effects are also positive in humans

Rheumatoid arthritis, tests on a new therapy with fewer side effects are also positive in humans

A new approach, born from the fusion between antibody and drug, has proven effective, both in mice and in humans, in calming the immune cells that drive inflammatory diseases, such as rheumatoid arthritis, avoiding the typical side effects of drugs conventional. This was revealed by an international study, published in Science Translational Medicine. The results open the way to overcoming an important obstacle relating to the safety of the clinical use of glucocorticoids, which are among the most used drugs for inflammatory disorders. Although glucocorticoids are effective, they cannot be taken for a long time, as they cause side effects, such as bone fractures, increased blood sugar, glaucoma and others.

A more effective therapy with fewer side effects

The occurrence of such side effects is due to the systemic nature of most standard glucocorticoids. To find a strategy capable of limiting the effects of drugs and therefore enhancing their clinical usefulness, Michael McPhersonof the AbbVie Bioresearch Center, together with his colleagues, have developed a new approach that allows us to overcome this complication: thanks to a compound that involves the association between antibody and drug, which combines the properties of homing of antibodies, i.e. the continuous migration of lymphocytes between the bloodstream, lymphatic vessels, secondary lymphoid tissues and non-peripheral lymphoid tissues, with the therapeutic effects of a drug.

The test on mice

The result is a drug conjugate, i.e. a therapeutic approach that in addition to the active part, contains a substance that increases its effectiveness. This, called ABBV-3373, fuses an antibody against TNF, a protein that appears on the surface of active immune cells, with a compound that enhances the activity of the glucocorticoid receptor. This allows the conjugate to bind to TNF on overactive immune cells before being taken up by the cells themselves, where it releases the glucocorticoid receptor modulator to calm the cells’ inflammatory activities. A mouse version of ABBV-3373 significantly suppressed inflammatory signaling in mouse models with contact hypersensitivity or induced arthritis and completely inhibited arthritis for over 30 days, following a single dose.

The results on human volunteers

Studying serum samples from a Phase 1 study, the researchers also found that the conjugate showed favorable absorption properties in healthy volunteers. Notably, the human version of the conjugate did not dramatically affect systemic glucocorticoid markers in either volunteers or mice, supporting the idea of ​​a potential alternative as a safer and more sustainable anti-inflammatory tool.

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