Nanoparticle reduces skin and lung scarring for scleroderma, mouse study
finds
The findings provide promise of targeted treatment for patients with the disease
Date:
March 7, 2022
Source:
Michigan Medicine - University of Michigan
Summary:
Researchers found a unique immune cell plays a key role in the
chronic inflammation and scarring in the lungs and skin of people
with scleroderma, or systemic sclerosis. After injecting mice
with biodegradable PLG nanoparticles, which are used in medical
sutures, researchers found that the nanoparticles specifically
targeted these inflammatory cells and prevented skin and lung
fibrosis. Researchers say it's a promising step towards targeted
treatment for patients with early scleroderma.
FULL STORY ========================================================================== Investigators have discovered that a biodegradable nanoparticle used in
medical sutures could combat a rare, sometimes-fatal autoimmune disease.
========================================================================== Researchers found that a unique macrophage, an immune cell that removes bacteria or dead cells, plays a key role in the chronic inflammation and scarring in 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 around 70,000 Americans
and currently has no effective treatment.
The research team injected mice with biodegradable PLG nanoparticles,
short for poly (lactic-co-glycolic) acid. The results, published in JCI Insight, reveal that PLG specifically targeted MARCO+ inflammatory cells
and prevented skin and lung fibrosis. Even more striking, nanoparticle treatment could even reverse fibrosis in these mice, says John Varga,
M.D., senior author of the paper and chief of the Michigan Medicine
Division of Rheumatology.
"The findings reveal a stark difference: untreated mice had terrible
scarring in the lungs, and those treated with this nanoparticle saw the
disease decease in severity or completely disappear," said John Varga,
M.D., senior author of the paper and chief of the Michigan Medicine
Division of Rheumatology. "This is a promising step towards targeted
treatment for patients with early scleroderma that could potentially
mitigate the worst effects of the disease." The research team believes
the MARCO+ cells become activated in people with scleroderma and
circulate in the blood stream, traveling to the tissues and causing scar formation. While the PLG nanoparticle reduced fibrosis in mouse models,
Varga says future studies are needed to determine exactly how it prevents
the MARCO+ activation.
PLG is already approved by the U.S. Food and Drug Administration for
creating biodegradable sutures. In previous studies, Varga's co-authors
found that PLG decreased inflammation in mouse models of myocardial
infarction. It is not currently 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 for skin and lung thickening that impacts function, and we look for
any way to stop that from happening." Disclosures: Stephen D. Miller is
a co-founder of, member of the Scientific Advisory Board, grantee of, and
holds stock options in COUR Pharmaceutical Development Company and onCOUR Pharma, Inc., which holds the patent for the PLG nanoparticle technology.
Additional 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.
========================================================================== Story Source: Materials provided by
Michigan_Medicine_-_University_of_Michigan. Original written by Noah
Fromson. Note: Content may be edited for style and length.
========================================================================== Journal Reference:
1. Dan Xu, Swati Bhattacharyya, Wenxia Wang, Igal Ifergan, Ming-Yi
Alice
Chiang Wong, Daniele Procissi, Anjana Yeldandi, Swarna Bale,
Roberta G.
Marangoni, Craig Horbinski, Stephen D. Miller, John Varga. PLG
nanoparticles target fibroblasts and MARCO monocytes to
reverse multi- organ fibrosis. JCI Insight, 2022; DOI:
10.1172/jci.insight.151037 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/03/220307113040.htm
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