A potential new target for the treatment of rheumatoid arthritis has been discovered by scientists at NYU Langone Medical Center.
By enhancing the activity of immune cells that protect against runaway inflammation, the researchers have found a novel therapy for rheumatoid arthritis and other autoimmune diseases.
AdvertisementThe researchers found that treating these immune cells with an investigational drug wards off inflammation by holding a particular enzyme at bay.
"This is an unusual mechanism that could provide a potential therapeutic approach for the treatment of autoimmune diseases like rheumatoid arthritis or inflammatory diseases like Crohn's disease," said Michael Dustin, the Irene Diamond Professor of Immunology and professor of pathology at NYU Langone Medical Center.
Joint-destroying rheumatoid arthritis is generally considered an autoimmune disorder spurred on by the hyperactivity of conventional T cells that fight off infections, cancer, and other diseases.
Within the past few years, researchers at NYU and other institutions have learned that other immune system components known as regulatory T cells counterbalance the tendency of conventional T cells to become overactive, thus holding inflammation in check.
These regulatory T cells exert their influence by communicating with other parts of the immune system. Through molecular detective work and powerful microscopy, the new study's collaborators found that an enzyme known as protein kinase C theta is only partly activated in regulatory T cells.
When the regulatory cells are most active, in fact, most of the interfering enzyme is physically kept far away from the area important for cell-cell communication.
"It's a very unique distribution. In conventional T cells this enzyme is normally moved to the area where the cells are making contact. But in regulatory T cells, the enzyme is as far away as it can get from where the cells are communicating," Dustin said.
Based on that observation, the researchers began testing inhibitors of this kinase enzyme, including a molecule known as Compound 20 that had been in development by pharmaceutical company Boehringer Ingelheim. Surprisingly, the compound boosted the normal activity of regulatory T cells by about five-fold.
The researchers found that specifically blocking the activity of the kinase enzyme augmented the natural tendency of the regulatory T cell to keep it out of the communication channels. Thus, the compound enhanced the regulatory cells' anti-inflammation activity.
The study has been published in the March 25, 2010 online edition of Science.