Immune Tolerance in Autoimmune Disease
Autoimmune diseases occur when the immune system mistakenly flags certain cells in the body as foreign invaders. The resulting attack can cause irreparable damage to critical organs and tissues. For example, in multiple sclerosis, it’s the myelin coating that insulates nerve cells; in lupus, it can be any number of organs or systems that are damaged. Currently, many of the primary methods to treat patients with autoimmune disease utilize immune suppressors, which help reduce the inflammatory attack on tissues but can put patients at higher risk for developing infections.
Immune tolerance therapies are designed to stop, or even prevent, the autoimmune disease while leaving the body's disease-fighting abilities intact. These tolerance therapies essentially reprogram the immune system, so that a short course of treatment will have long-lasting, perhaps lifelong effects. While immune tolerance therapies are mainly experimental, the Immune Tolerance Network (ITN) believes that targeted reprogramming of the immune system holds a great deal of promise to effectively treat autoimmune diseases with fewer side effects than current drugs.
Research Focus - Autoimmune Disease
The clinical heterogeneity of the more than 80 autoimmune diseases presents a significant challenge with respect to the development of therapies designed to re-establish self-tolerance. The ITN’s approach to tolerance in autoimmune diseases attempts to address these challenges through a coordinated program of clinical studies aimed at establishing proof-of-principle either in diseases where a self-antigen has been identified, the target organ is accessible for further study or the disease pathogenesis has been relatively well established.
Given the complex nature of these diseases, and following the approaches being developed in the transplant and allergy portfolios, the ITN builds on results from ongoing trials by developing combination approaches affecting humoral and cellular, as well as adaptive and innate, immune responses. This includes combinations that ablate or anergize effector responses, deviate induced responses and boost regulatory responses. Because combination therapy trials can be logistically and scientifically challenging, the ITN has adopted the use of smaller, mechanistically-based studies as a first step in evaluating promising combinations and establishing a mechanistic plan that will inform on the pathways of tolerance.