Researchers have found that a biodegradable nanoparticle used in medical sutures can fight a rare, sometimes fatal, autoimmune disease.
Researchers have found that a unique macrophage, an immune cell that eliminates bacteria or dead cells, plays a key role in the chronic inflammation and scarring of the lungs and skin of people with scleroderma or systemic sclerosis. This macrophage, called MARCO+, was found to be elevated in people with the orphan disease, which affects about 70,000 Americans and currently has no effective treatment.
The research team injected mice with nanoparticles of biodegradable PLG, short for poly(lactic-co-glycolic) acid. The results, published in JCI Overview, reveal that PLG specifically targeted inflammatory MARCO+ cells and prevented skin and lung fibrosis. Even more strikingly, nanoparticle treatment might even reverse fibrosis in these mice, says John Varga, MD, lead author of the paper and chief of the Michigan Medicine Division of Rheumatology.
“The results reveal a striking difference: untreated mice had terrible scarring in the lungs, and those treated with this nanoparticle saw the disease decrease in severity or disappear completely,” said John Varga, MD, lead author of the article and head of Michigan. Department of rheumatology medicine. “This is a promising step towards a targeted treatment for patients with early onset scleroderma that could potentially mitigate the worst effects of the disease.”
The research team believe that MARCO+ cells become activated in people with scleroderma and circulate in the bloodstream, traveling to tissues and causing scarring. While the PLG nanoparticle reduced fibrosis in mouse models, Varga says future studies are needed to determine exactly how it prevents MARCO+ activation.
PLG is already approved by the United States Food and Drug Administration for creating biodegradable sutures. In previous studies, Varga’s co-authors found that PLG reduced inflammation in mouse models of myocardial infarction. It is currently not available as a treatment for patients.
“We hope that this type of therapy will one day be evaluated in clinical trials for scleroderma,” Varga said. “People with scleroderma are at great risk of thickening of the skin and lungs which affects function, and we are all looking for ways to prevent this from happening.”
Disclosures: Stephen D. Miller is co-founder, scientific advisory board member, beneficiary, and holds stock options in COUR Pharmaceutical Development Company and onCOUR Pharma, Inc., which holds the patent for the PLG nanoparticle technology .
Other authors include Swati Bhattacharyya, Swarna Bale, both of Michigan Medicine, and Dan Xu, Wenxia Wang, Igal Ifergan, Ming-Yi Alice Chiang Wong, Daniele Procissi, Anjana Yeldandi, Robert G Marangoni, Craig Horbinski, and Stephen D. Miller, all of Northwestern University Feinberg School of Medicine.
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Material provided by Michigan Medicine – University of Michigan. Original written by Noah Fromson. Note: Content may be edited for style and length.