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NIH Report: Research Breakthrough Selectively Suppresses Immune System

Scientists develop new treatment to combat autoimmune disease in animal model (Nov. 18)

Researchers funded by the National Institutes of Health (NIH) have developed new technology to selectively inhibit the part of the immune system responsible for attacking myelin — the insulating material that encases nerve fibers and facilitates electrical communication between brain cells — in a mouse model of multiple sclerosis (MS).

Autoimmune disorders occur when T-cells — a type of white blood cell within the immune system — mistake the body’s own tissues for a foreign substance and attack them. Current treatment for autoimmune disorders involves the use of immunosuppressant drugs, which inhibit the overall activity of the immune system. However, these medications leave patients susceptible to infections and increase their risk of cancer as the immune system’s normal ability to identify and destroy aberrant cells within the body is compromised.

Supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) at the NIH, researchers at Northwestern University in Evanston, Illinois, teamed up with scientists at the University of Sydney in Australia and at the Myelin Repair Foundation in Saratoga, California, to develop a novel way of repressing only the part of the immune system that causes autoimmune disorders while leaving the rest of the system intact.

The new research takes advantage of a natural safeguard used by the body to prevent autoreactive T-cells — which recognize and have the potential to attack the body’s healthy tissues — from becoming active.

The findings were reported in the November 18 online edition of Nature Biotechnology.

The body has natural mechanisms for stopping inappropriate immune responses. One of these mechanisms involves the ongoing clearance of apoptotic cells from the body. When a cell dies, it releases chemicals that attract immune-system macrophages. These macrophages gobble up the dying cell and deliver it to the spleen, where it presents self-antigens — tiny portions of proteins from the dying cell — to a pool of T-cells. To prevent autoreactive T-cells from being activated, macrophages initiate the repression of any T-cells capable of binding to the self-antigens.

Dr. Stephen Miller at Northwestern University was the first to demonstrate that by coupling a specific self-antigen, such as myelin, to apoptotic cells, investigators could tap into this natural mechanism to suppress T-cells that would normally attack the myelin. Miller and his colleagues spent decades demonstrating that they could generate antigen-specific immune suppression in various animal models of autoimmune diseases. Recently, they initiated a preliminary clinical trial with collaborators in Germany to test the safety of injecting the antigen-bound apoptotic cells into patients with MS. While the trial successfully demonstrated that the injections were safe, it also highlighted key problems with using cells as a vehicle for antigen delivery: the procedure is costly, difficult, and time-consuming.

Therefore, the researchers looked into the possibility of developing a surrogate for the apoptotic cells. After trying out various formulations, Miller’s laboratory successfully linked the desired antigens to microscopic, biodegradable particles, which they predicted would be taken up by circulating macrophages similar to apoptotic cells. The material that makes up the particles has been approved by the FDA and is currently used in resorbable sutures as well as in clinical trials to deliver anti-cancer agents.

When tested, the antigen-bound particles turned out to be as good as, if not better, than apoptotic cells at inducing T-cell tolerance in animal models of autoimmune disorders.

Using their myelin-bound particles, the researchers were able to prevent the initiation of MS in their mouse model as well as to inhibit its progression when injected immediately following the first sign of clinical symptoms.

In addition to its potential use for the treatment of MS, the researchers have shown in the laboratory that their new therapy can induce tolerance for other autoimmune diseases, such as type I diabetes and specific food allergies. They also speculate that transplant patients could benefit from the treatment, which has the potential to retract the body’s natural immune response against a transplanted organ.

Source: NIBIB; November 18, 2012.

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