Nanotech strategy shows promise for treating autoimmune diseases – ScienceDaily

Scripps Research scientists have reported success in initial testing of a new nanotechnology-based strategy against autoimmune diseases.

The scientists, who published their results in the journal on November 23, 2022 ACS nano, engineered cell-like “nanoparticles” that target only the immune cells that drive an autoimmune response, leaving the rest of the immune system intact and healthy. The nanoparticles were highly retarding and in some animals even prevented severe disease in a mouse model of arthritis.

“The potential benefit of this approach is that it would allow safe long-term treatment of autoimmune diseases, in which the immune system attacks its own tissues or organs – using a method that does not cause widespread immune suppression, as is the case with current treatments.” . says study leader James Paulson, PhD, Cecil H. and Ida M. Green Chair in Chemistry in the Department of Molecular Medicine at Scripps Research.

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

Paulson and his team took an approach that more closely targets the immune system. Many autoimmune diseases are triggered or fueled by immune attacks on just one protein in the patient’s body known as “self-antigen.” The idea underlying the nanoparticle strategy is to eliminate or deactivate only those immune cells that attack this self-antigen – an approach that could be at least as effective as broad immunosuppression without the side effects. Autoimmune diseases that are dominated by immune responses to a single self-antigen include some forms of arthritis, the skin blister disease known as pemphigus, and Graves’ disease, a thyroid condition.

The researchers, including first author Katarzyna Brzezicka, PhD, a postdoctoral researcher in the Paulson lab, research assistant Britni Arlian, and other lab members, designed nanoparticles that could disable two types of immune cells: B cells and T cells. On its surface, each nanoparticle carried copies of a target self-antigen and a sugar-related molecule that can bind to a special ‘switch’ receptor on B cells called CD22. B cells, which produce antibodies and are specific for various antigens, effectively shut down when they encounter both the particular antigen they are targeting and the binding partner of CD22 at the same time.

Each nanoparticle has also been spiked with a powerful compound called rapamycin to stimulate the production of immune cells called regulatory T cells. TReg Cells, as they are also called, are responsible for suppressing other T cells that are needed for an autoimmune attack. The overall goal of the study was to effectively knock out only the B and T cells that recognize the self antigen, leaving the rest of the B and T cell populations intact.

The researchers first showed that their nanoparticle-based strategy could allow the mouse’s immune system to tolerate a chicken protein, ovalbumin, which would otherwise elicit a strong response. Next, they tested the strategy in a widely used mouse model of arthritis, in which the mouse’s immune system is genetically predisposed to attack a self-antigen called GPI. The scientists showed that treating the mice with GPI-tolerant nanoparticles at three weeks of age greatly delayed the development of signs of arthritis, which would normally appear a week or two later. In fact, about a third of the mice remained arthritis-free for the maximum follow-up period of 300 days. Tests confirmed that the treatment drastically reduced the production of anti-GPI antibodies in mice while reducing their TReg populations.

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

“We were able to ‘cure’ a third of these animals in this early demonstration, and I think there is potential to combine our nanoparticles with other immunomodulator treatments to make them even more effective,” says Paulson. “So that will be our next step – as well as demonstrating our technology against other autoimmune diseases that are caused by unwanted immune responses to a self-antigen.”

“Suppression of Autoimmune Rheumatoid Arthritis with Hybrid Nanoparticles That Induce B and T Cell Tolerance to Self-Antigen” was co-authored by Katarzyna Brzezicka, Britni Arlian, Shengyang Wang, Merissa Olmer, Martin Lotz, and James Paulson, all of Scripps Research.

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

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