Compound Keeps Inflammation in Check

Scientists at NYU Langone Medical Center may have found a new therapy for rheumatoid arthritis and other autoimmune diseases.

The researchers published the results of a study focused on the use of an investigational drug to treat the diseases in the online edition of Science.

The drug wards off inflammation by holding a particular enzyme at bay.

Rheumatoid arthritis is spurred on by the hyperactivity of conventional T cells that fight off infections, cancer, and other diseases. Recent research demonstrates that regulatory T cells counterbalance the tendency of conventional T cells to become overactive, which keeps inflammation from developing.

The new study found that an enzyme called protein kinase C theta is only partly activated in regulatory T cells. When these regulatory cells are most active the interfering enzyme is physically kept far away from the area important for cell-cell communication.

The researchers tested inhibitors of the enzyme, including Compound 20, which had been in development by pharmaceutical company Boehringer Ingelheim. The compound boosted the normal activity of regulatory T cells by almost five-fold. When the activity was blocked the enzyme augmented the natural tendency of the regulatory T cell to keep it out of the communication channels. The compound enhanced the regulatory cells’ anti-inflammation activity.

An abnormally low level of regulatory T cells is normally found in patients with rheumatoid arthritis. The study results demonstrated that correlation by examining the blood of 25 patients with varying degrees of RA, which showed low levels of the cells. Yet, when the enzyme inhibitor was given to these patients the defective regulatory cells were revived and their levels increased to those of normal healthy individuals.

The Compound 20 inhibitor was also tested in a group of mice with Crohn’s disease. The results demonstrated that the inhibitor the anti-inflammatory activity within the mice increased tremendously, essentially protecting the mice from the disease.