Nano-strategy shows promise in treating autoimmune diseases – ScienceDaily

Scientists at Scripps Research report success in preliminary tests of a new nanotechnology-based strategy against autoimmune diseases.

Scientists who published their findings on November 23, 2022 in the journal ACS Nano, engineered nanoparticles that target only the immune cells that trigger the autoimmune reaction, leaving the rest of the immune system intact and healthy. Nanoparticles significantly delayed and, in some animals, prevented severe disease in a mouse model of arthritis.

“The potential advantage of this approach is that it would enable safe, long-term treatment of autoimmune diseases where the immune system attacks its own tissues or organs — using a method that will not cause widespread immunosuppression, as current therapies do,” says study senior author James Paulson, MD. Ph.D., Cecil H, and Ida M. Green Chair in Chemistry in the Department of Molecular Medicine at Scripps Research.

Autoimmune diseases such as rheumatoid arthritis occur when the immune system mistakenly attacks a person’s tissues or organs. These diseases affect an estimated 10 million people in the United States alone. Treatments are available and can be effective for many patients, but they tend to suppress the immune system indiscriminately, leading to increased susceptibility to infections and cancers — among other side effects.

Paulson and his team took an approach that targeted the immune system more specifically. Many autoimmune diseases result from immune attacks on just one protein in the patient’s body, known as an autoantigen. The idea behind the nanoparticle strategy is to eliminate or just inactivate the immune cells that attack this self-antigen — an approach that could be at least as effective as broad immune suppression, without the side effects. Autoimmune diseases that are dominated by immune responses to a single autoantigen include some forms of arthritis, the blister skin disease known as pemphigus, and Graves’ disease of the thyroid gland.

The researchers, including first author Katarzyna Brygica, PhD, a postdoctoral researcher in Paulson’s lab, research assistant Brittney Arlean, and other members of the lab, designed nanoparticles that can disable two types of immune cells: B cells and T cells. On its surface, each nanoparticle carries copies of its target self-antigen, as well as a sugar-binding molecule that can bind to a special ‘off’ receptor on B cells called CD22. B cells, which make antibodies and are specific to different antigens, will effectively shut themselves off if they encounter both the specific antigen they target and the binding partner of CD22 at the same time.

Each nanoparticle has also been linked to a powerful compound called rapamycin to stimulate the production of immune cells called regulatory T cells. treg T cells, as they are also known, are responsible for suppressing other T cells needed to generate an autoimmune attack. The overall aim of the study was to effectively eliminate only the self-antigen-recognizing B and T cells, leaving the rest of the B and T cell populations intact.

The researchers first showed that their nanoparticle-based strategy could tolerate a mouse immune system to a chicken protein, albumin ovalbumin, that would trigger a robust response. Next, they tested the strategy in a widely used mouse model of arthritis, in which a mouse’s immune system is genetically predisposed to attack an autoantigen called a GPI. Scientists have shown that treating mice with GPI-tolerant nanoparticles at the age of three weeks significantly delayed the onset of signs of arthritis that usually appear after one or two weeks. In fact, about a third of the mice remained free of arthritis for a maximum follow-up time of 300 days. Tests confirmed that the treatment significantly reduced the mice’s production of anti-GPI antibodies, and at the same time boosted testosterone.reg population.

Paulson says his team plans to follow up these very promising results with further refinement of the nanoparticle strategy.

“We were able to ‘cure’ a third of these animals at this early showing, and I think there is potential to combine the nanoparticles with other immunotherapies to make them more effective,” Paulson says. “This is our next step – in addition to demonstrating our technology against other autoimmune diseases caused by unwanted immune responses to a self-antigen.”

“Suppression of Autoimmune Rheumatoid Arthritis with Hybrid Nanoparticles Inducing B- and T-Cell Tolerance To Self-Antigen” is co-authored by Katarzyna Przysica, Brittney Arlian, Xinjiang Wang, Merissa Ulmer, Martin Lutz, and James Paulson, all from Scripps Research.

This work was funded in part by the National Institutes of Health (R01AI050143, R01AI132790).

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