Scientists at Scripps Analysis have reported success in preliminary checks of a brand new, nanotech-based technique towards autoimmune ailments.
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 tremendously delayed, and in some animals even prevented, extreme illness in a mouse mannequin of arthritis.
“The potential benefit of this strategy is that it might allow protected, long-term therapy for autoimmune ailments 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 Medication at Scripps Analysis.
Autoimmune ailments corresponding to rheumatoid arthritis are induced when the immune system mistakenly assaults an individual’s personal tissues or organs. These diseases have an effect on an estimated 10 million folks within the U.S. alone. Remedies can be found and may 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 negative effects.
Paulson and his staff have taken an strategy that targets the immune system extra narrowly. Many autoimmune ailments 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 remove or deactivate solely the immune cells that assault that self-antigen — an strategy that could possibly be at the least as efficient as broad immune suppression, with out the negative effects. Autoimmune ailments which might be 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 would deactivate two forms 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 totally different antigens, will successfully shut themselves off in the event that they encounter each the actual antigen they aim and the binding accomplice of CD22 on the similar time.
Every nanoparticle additionally was laced with a robust compound known as rapamycin to stimulate the manufacturing of immune cells known as regulatory T cells. Treg cells, as they’re additionally recognized, are answerable for suppressing different T cells wanted to generate an autoimmune assault. The general intention 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 may tolerize the mouse immune system to a rooster protein, ovalbumin, that might in any other case set off a powerful 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 therapy of the mice with GPI-tolerizing nanoparticles on the age of three weeks tremendously delayed the event of arthritis indicators that might usually seem per 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 therapy dramatically decreased the mice’s manufacturing of anti-GPI antibodies, and on the similar 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 have been capable of ‘treatment’ a 3rd of those animals on this early demonstration, and I believe 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 expertise towards different autoimmune ailments brought on by 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 partly by the Nationwide Institutes of Well being (R01AI050143, R01AI132790).