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Scientists at Scripps Analysis have reported success in preliminary assessments of a brand new, nanotech-based technique in opposition to autoimmune illnesses.
The scientists, who reported their outcomes on November 23, 2022, within the journal ACS Nano, engineered cell-like “nanoparticles” that focus on solely the immune cells driving an autoimmune response, leaving the remainder of the immune system intact and wholesome. The nanoparticles vastly delayed, and in some animals even prevented, extreme illness in a mouse mannequin of arthritis.
“The potential benefit of this method is that it will allow secure, long-term remedy for autoimmune illnesses the place the immune system assaults its personal tissues or organs — utilizing a technique that will not trigger broad immune suppression, as present therapies do,” says research senior writer James Paulson, PhD, Cecil H. and Ida M. Inexperienced Chair of Chemistry within the Division of Molecular Drugs at Scripps Analysis.
Autoimmune illnesses resembling rheumatoid arthritis are brought on when the immune system mistakenly assaults an individual’s personal tissues or organs. These diseases have an effect on an estimated 10 million individuals within the U.S. alone. Therapies can be found and will be efficient for a lot of sufferers, however they have a tendency to suppress the immune system indiscriminately, creating an enhanced susceptibility to infections and cancers — amongst different unwanted effects.
Paulson and his staff have taken an method that targets the immune system extra narrowly. Many autoimmune illnesses are triggered or pushed by immune assaults on only one protein within the affected person’s physique, referred to as a “self-antigen.” The concept underlying the nanoparticle technique is to get rid of or deactivate solely the immune cells that assault that self-antigen — an method that may very well be no less than as efficient as broad immune suppression, with out the unwanted effects. Autoimmune illnesses which are dominated by immune responses to a single self-antigen embody some types of arthritis, the pores and skin blister illness referred to as pemphigus and the thyroid ailment Graves’ illness.
The researchers, together with first writer Katarzyna Brzezicka, PhD, a postdoctoral analysis affiliate within the Paulson lab, analysis assistant Britni Arlian, and different lab members, designed nanoparticles that might deactivate two sorts of immune cells: B cells and T cells. On its floor, every nanoparticle bore copies of a goal self-antigen, plus a sugar-related molecule that may bind to a particular “off swap” receptor on B cells known as CD22. B cells, which make antibodies and are particular to completely different antigens, will successfully shut themselves off in the event that they encounter each the actual antigen they aim and the binding associate of CD22 on the identical time.
Every nanoparticle additionally was laced with a strong compound known as rapamycin to stimulate the manufacturing of immune cells known as regulatory T cells. Treg cells, as they’re additionally identified, are answerable for suppressing different T cells wanted to generate an autoimmune assault. The general goal of the research was to successfully knock out solely the B and T cells that acknowledge the self-antigen, leaving the remainder of the B- and T-cell populations intact.
The researchers first demonstrated that their nanoparticle-based technique might tolerize the mouse immune system to a hen protein, ovalbumin, that may in any other case set off a robust response. Subsequent, they examined the technique in a broadly used mouse mannequin of arthritis, during which the mouse immune system is genetically predisposed to assault a self-antigen known as GPI. The scientists confirmed that remedy of the mice with GPI-tolerizing nanoparticles on the age of three weeks vastly delayed the event of arthritis indicators that may usually seem every week or two later. Actually, a few third of the mice remained arthritis-free for the utmost follow-up interval of 300 days. Assessments confirmed that the remedy dramatically decreased the mice’s manufacturing of anti-GPI antibodies, and on the identical time boosted their Treg populations.
Paulson says his staff plans to comply with up these extremely promising outcomes with additional optimization of the nanoparticle technique.
“We had been capable of ‘remedy’ a 3rd of those animals on this early demonstration, and I feel there’s the potential to mix our nanoparticles with different immune modulator therapies to make it much more efficient,” Paulson says. “So that may our subsequent step — in addition to demonstrating our know-how in opposition to different autoimmune illnesses attributable to undesirable 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 Analysis.
This work was funded partially by the Nationwide Institutes of Well being (R01AI050143, R01AI132790).
