New target for rheumatoid arthritis identified
Researchers at Hospital for Special Surgery have discovered a new target in the treatment of rheumatoid arthritis. They are investigating a protein (IRHOM2) that could be an alternative to tumor necrosis factor alpha blockers (TNF blockers). Rheumatoid arthritis is a systemic autoimmune disease, that affects approximately 1% of the world population. This disease mainly involves joint damage, but it can affect other parts of the body such as the pleura, pericardium, kidneys, skin, etc..
In rheumatoid arthritis, systemic inflammatory response is generated mainly by TNF-alpha, a protein that is involved in several inflammatory diseases. When produced in excessive amounts, TNF alpha leads to inappropriate activation of the immune system resulting in inflammation. Based on this hypothesis, researchers have thought that this could be an effective therapeutic target in the treatment of rheumatoid arthritis. Therefore, there are a number of TNF alpha blockers: etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), which help patients suffering from this disease.
However, treatment based on TNF alpha inhibitors has several disadvantages, such as that it is quite expensive. In addition, as with any medication, not all patients respond to treatment. Therefore, the necessity of a new therapeutic alternative that could help patients with this disease. In the study, researchers found that TNF alpha works with another protein called TACE (TNF-alpha converting enzyme), and they thought that blocking TACE would have the same effect as blocking TNF-alpha. But it seems that without the TACE patients are prone to intestinal infections and skin lesions.
Another discovery was that these proteins are regulated by some molecules TACE called IRHOM1 and IRHOM2 and it seems that the absence of IRHOM2 inhibits TNF alpha release. Furthermore, experiments on laboratory animals have shown that rats that did not have IRHOM2, did not develop skin infections or intestinal lesions. Therefore, the next step was to test whether blocking IRHOM2 would protect against the disease. Indeed, the results showed that mice genetically engineered to be deficient in IRHOM2 did not develop rheumatoid arthritis. “With IRHOM2, we have a unique and unprecedented opportunity to inactive TACE only in certain cell types, and not in others, and there is currently no other effective way of doing that”, said Carl Blobel, M.D., Ph.D., program director of the Arthritis and Tissue Degeneration Program at HSS.
This means that if scientists could find antibodies or pharmacological compounds to block TACE function in immune cells, patients with rheumatoid arthritis could benefit from a new treatment. Dr. Jane Salmon, an author of the study, said that these compounds would theoretically have less toxicity than TNF alpha blockers because they block TNF alpha release only in the cells involved in inflammation.