A new study from researchers in South Carolina report that a small protein called M10 peptide might prevent fibrosis (scarring) in people with systemic sclerosis (SSc). M10 could be especially useful for treating interstitial lung diseases (ILD), the most severe complication of SSc.
The report, “M10, a caspase cleavage product of the hepatocyte growth factor receptor, interacts with Smad2 and demonstrates antifibrotic properties in vitro and in vivo,“ appeared in the journal Translational Research.
SSc is a connective tissue disease affecting many different systems within the body, including the lungs. It is characterized by diseased blood vessels and fibrosis — the thickening and scarring of connective tissue.
“Systemic sclerosis is often more than skin deep, affecting the gastrointestinal tract, the lungs, the heart, the kidneys, and the blood vessels, so it is a model for many other more prevalent fibrotic diseases,” said the study’s co-author Richard M. Silver, M.D., in a press release.
Silver is director of the Division of Rheumatology and Immunology at the Medical University of South Carolina (MUSC). “Whereas there may be 300,000 Americans with scleroderma/systemic sclerosis, millions of others suffer from fibrosis of these other organ systems,” he said.
M10 is a very small molecule made up of only 10 amino acids, the building blocks of proteins. The researchers studied a mouse model of lung fibrosis, induced by the drug bleomycin. When scientists injected M10 into the mice, it prevented lung fibrosis. When the mice received a random “scrambled” molecule containing 10 amino acids, the lung scarring still occurred. This showed that M10 has very specific effects.
The experiments demonstrated that M10 acts through a naturally occurring immune system molecule called transforming factor beta 1 (TGF-β1) by blocking it. TGF-β1 is one factor that can contribute to lung scarring. Other influences of M10 may include preventing collagen deposits from forming, based on in vitro experiments (cells grown in a dish).
“We observed that treatment with M10 by intraperitoneal injection markedly improved bleomycin-induced lung fibrosis in mice, suggesting that the M10 peptide may have potential for use in the treatment of scleroderma-associated interstitial lung disease and other forms of pulmonary fibrosis, for example, idiopathic pulmonary fibrosis,” concluded Galina S. Bogatkevich, M.D., Ph.D., the study senior author.
Bogatkevich and colleagues will continue to study M10 in animals, and the scientists hope to eventually proceed to human clinical trials.