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Nanotech strategy shows promise to treat autoimmune disease

ANI | Updated: Dec 02, 2022 06:21 IST

California [US], December 2 (ANI): Scripps Research scientists have reported success in preliminary tests of a new nanotech-based strategy for treating autoimmune diseases.
The researchers created cell-like "nanoparticles" that target only the immune cells causing an autoimmune reaction, leaving the rest of the immune system intact and healthy.
They published their findings in the journal ACS Nano.
In a mouse model of arthritis, the nanoparticles significantly delayed, and in some cases prevented severe disease.
"The potential advantage of this approach is that it would enable safe, long-term treatment for autoimmune diseases where the immune system attacks its own tissues or organs--using a method that won't cause broad immune suppression, as current treatments do," says senior study author James Paulson, PhD, Cecil H. and Ida M. Green Chair of Chemistry in the Department of Molecular Medicine at Scripps Research.
Autoimmune diseases, such as rheumatoid arthritis, occur when the immune system incorrectly attacks the body's own tissues or organs. These diseases affect an estimated ten million people in the United States alone. Treatments are available and can help many patients, but they tend to suppress the immune system indiscriminately, increasing susceptibility to infections and cancer, among other side effects.
Paulson and his colleagues have taken a more targeted approach to the immune system. Many autoimmune diseases are caused or exacerbated by immune attacks on a single protein in the patient's body, referred to as a "self-antigen."

The idea underlying the nanoparticle strategy is to eliminate or deactivate only the immune cells that attack that self-antigen--an approach that could be at least as effective as broad immune suppression, without the side effects. Autoimmune diseases dominated by immune responses to a single self-antigen include some forms of arthritis, the skin blister disease known as pemphigus and the thyroid ailment Graves' disease.
The researchers developed nanoparticles that could deactivate two types of immune cells: B cells and T cells, with the help of first author Katarzyna Brzezicka, PhD, a postdoctoral research associate in the Paulson lab, research assistant Britni Arlian, and other lab members.
Each nanoparticle had copies of a target self-antigen on its surface and a sugar-related molecule that can bind to a special "off switch" receptor on B cells called CD22. B cells, which produce antibodies and are specific to different antigens, will effectively shut down if they come into contact with both the antigen they are looking for and the CD22 binding partner at the same time.
Each nanoparticle also was laced with a powerful compound called rapamycin to stimulate the production of immune cells called regulatory T cells.
Treg cells, as they're also known, are responsible for suppressing other T cells needed to generate an autoimmune attack. The overall aim 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 demonstrated that their nanoparticle-based strategy could tolerate a chicken protein, ovalbumin, that would otherwise elicit a strong immune response in mice. The strategy was then tested in a widely used mouse model of arthritis in which the mouse immune system is genetically predisposed to attack a self-antigen known as GPI.
The researchers demonstrated that treating mice with GPI-tolerizing nanoparticles at the age of three weeks significantly delayed the development of arthritis symptoms, which would normally appear a week or two later. In fact, approximately one-third of the mice remained arthritis-free for the entire 300-day follow-up period. Tests confirmed that the treatment significantly reduced the mice's production of anti-GPI antibodies while also increasing their Treg populations.
Paulson says his team plans to follow up these highly 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's the potential to combine our nanoparticles with other immune modulator treatments to make it even more effective," Paulson says. "So that will be our next step--as well as demonstrating our technology against other autoimmune diseases caused by unwanted immune responses to a self-antigen." (ANI)