Use of PLGA-ATRA MP as a potential disease-modifying agent to treat autoimmune arthritis

To combat rheumatoid arthritis, a team of engineers at the University of California, San Diego has created a biodegradable polymer system that works in tandem with the body’s immune system. The study was published in Advanced Science

McBride and his team reported a promising line of research using an immunoregulatory strategy based on the prolonged joint-localized release of all-trans retinoic acid (ATRA). ATRA is a tiny molecule that the FDA has currently approved for use in treating acute promyelocytic leukemia (APML). Twenty years of research suggest that it could be useful in autoimmune arthritis treatment and inflammation reduction. This strategy controls systemic disease through modulation of local immunological activation, enhancement of disease-protective T cells, and sustained joint-localized release of ATRA. 

After intra-articular (IA) injection, sustained release poly-(lactic-co-glycolic acid (PLGA)-based biodegradable microparticles encasing ATRA (PLGA-ATRA MP) are retained in arthritic mice joints. IA PLGA-ATRA MP boosts migratory Treg, which reduces inflammation and modifies disease in both injected and uninjected joints, a feature that is likewise replicated by IA injection of Treg. In the SKG and collagen-induced arthritis animal models, PLGA-ATRA MP decreases proteoglycan loss and bone erosions. Surprisingly, PLGA-ATRA MP does not cause generalized immune suppression because of its modulation of systemic illness. PLGA-ATRA MP may one day be used to treat autoimmune arthritis by altering the diseases.

In rheumatoid arthritis, patients’ immune system recognizes this ATRA as a target for attack and sends a massive amount of additional immune cells to fight the infection there until it is completely eradicated. The disease site is then turned into a factory that produces regulatory T cells It enables the timed release of ATRA, which rewires T cells to treat disease, using a biodegradable biomaterial. They retain the capacity to recognize and activate in the joints, reducing inflammation rather than stimulating the recruitment of additional immune cells. Since repeated injections are not recommended in areas like joints, the sustained-release formulation offers sufficient therapeutic exposure to tip the scales.

The long-lasting modifications brought about by ATRA to the cellular machinery’s capacity to read cell DNA improve the anti-inflammatory regulatory T-cell function. To treat T cells where the disease is evident, regulatory T cells are created that are specific to the afflicted area. This study still contains significant flaws, thus more research is necessary.

Reference

  1. McBride DA, Kerr MD, Johnson WT, Nguyen A, Zoccheddu M, Yao M, Prideaux EB, Dorn NC, Wang W, Svensson MN, Bottini N. Immunomodulatory Microparticles Epigenetically Modulate T Cells and Systemically Ameliorate Autoimmune Arthritis. Advanced Science. 2023 Apr;10(11):2202720.
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