A team of researchers from Scripps Research announces successful preliminary tests of a new nanotechnology-based approach against autoimmune diseases on November 23rd2022, number of ACS Nano.
Scientists have engineered cell-like “nanoparticles” that only attack immune cells, triggering an autoimmune reaction, leaving the rest of the immune system unharmed. Nanoparticles significantly delayed, and even stopped in a few animals, critical 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 where the immune system attacks its own tissues or organs, using a method that will not cause large-scale immune suppression, as current treatments do.
James Paulson, Ph.D., Study Lead Author and Chair Cecil H. and Ida M. Green, Department of Molecular Medicine, Scripps Research
Autoimmune diseases such as rheumatoid arthritis occur when the immune system mistakenly attacks a person’s own organs or tissues. These diseases affect nearly 10 million people in the United States alone
Treatments are there and can be effective for many patients, but they tend to arbitrarily overpower the immune system, leading to greater susceptibility to cancers and infections, among other complications.
Paulson and his team used an approach that attacks the immune system more tightly. Many autoimmune diseases are caused or provoked by immune attacks against a single protein in the patient’s body, called the “autoantigen”.
The idea behind the nanoparticle approach is to eliminate or neutralize only those immune cells that target this self-antigen. This method could be at least as effective as broad immune suppression without the complications.
Autoimmune diseases controlled by immune responses to a single autoantigen include a few types of arthritis, a skin blistering disease called pemphigus, and the thyroid disease, Graves’ disease.
Scientists, including study first author Katarzyna Brzezicka, Ph.D., a postdoctoral research associate at the Paulson lab, research assistant Britni Arlian and other members of the lab, designed nanoparticles capable of neutralize two types of immune cells: T cells and B cells.
On its surface, each nanoparticle contained copies of a target self-antigen, as well as a sugar-associated molecule that can adhere to a dedicated “off switch” receptor on B cells known as CD22. B cells, which create antibodies and are specific for various antigens, will successfully isolate if they simultaneously encounter the specific antigen they are targeting and the binding partner of CD22.
Each nanoparticle has also been mixed with a powerful compound called rapamycin to trigger the creation of immune cells called regulatory T cells. Jregister cells, as they are also called, are responsible for defeating other T cells needed to generate an autoimmune attack.
The overall goal of the study was to successfully eliminate only B and T cells that identify the self-antigen, leaving other B and T cell populations intact.
The scientists first showed that their nanoparticle-based approach could tolerate the mouse immune system to a chicken protein, ovalbumin, which would otherwise stimulate a potent response.
Next, they tested the approach in a widely used mouse model of arthritis, in which the mouse immune system is genetically inclined to attack a self-antigen known as GPI. The researchers demonstrated that treating mice with GPI-tolerant nanoparticles at three weeks of age significantly delayed the progression of signs of arthritis that typically appeared a week or two later.
About a third of the mice remained arthritis-free for most of the 300-day follow-up period. Tests verified that the treatment clearly decreased the mice’s generation of anti-GPI antibodies and simultaneously improved their Tregister populations.
Paulson says his team hopes to follow up these extremely encouraging results with further optimization of the nanoparticle approach.
“We were able to ‘cure’ a third of these animals in this first demonstration, and I think it is possible to combine our nanoparticles with other immune-modulating treatments to make them even more effective,” he said. added. said Paulson.
This will therefore be our next step, as well as the demonstration of our technology against other autoimmune diseases caused by adverse immune responses to a self-antigen.
James Paulson, Ph.D., Study Lead Author and Chair of Cecil H. and Ida M. Green, Department of Molecular Medicine, Scripps Research
The study was co-authored by Britni Arlian, Katarzyna Brzezicka, Shengyang Wang, Martin Lotz, Merissa Olmer and James Paulson, all of Scripps Research.
This study was partially funded by the National Institutes of Health (R01AI050143 and R01AI132790).
Brzezicka, KA, et al. (2022) Suppression of autoimmune rheumatoid arthritis with hybrid nanoparticles that induce B and T cell tolerance to self-antigen. ACS Nano. doi.org/10.1021/acsnano.2c05643.
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