MT-7117 reduces scleroderma symptoms in a mouse model

Experimental MT-7117 therapy reduces lung inflammation, skin fibrosis (scarring), and vascular dysfunction in a mouse model of plaque sclerosis (SSc), a study found.

“MT-7117 shows disease-modifying effects in preclinical models of SSc,” the researchers wrote. “The results of the current study indicate that MT-7117 is a potential therapeutic agent for SSc.”

The efficacy and tolerability of MT-7117, developed by Mitsubishi Tanabe Pharma, is currently being investigated in Phase II Clinical Trial (NCT04440592). Recruitment continues in the United States, Canada and Europe.

the study, “Dersimelagon, a novel oral melanocortin 1 receptor agonist, demonstrates disease-modifying effects in preclinical models of systemic sclerosis.And thePosted in Arthritis research and treatment.

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SSc, or scleroderma, is an autoimmune disease characterized by inflammation, abnormality of small blood vessels, and extensive scarring of multiple organs, including the skin and lungs. Currently approved treatments treat SSc-associated interstitial lung disease (ILD), the leading cause of death in people with SSc, but there are no approved treatments for the same condition.

Melanocortin receptors (MCR) are a family of proteins in various tissues in the body. It is present in inflammatory cells, such as monocytes, as well as the skin and cells lining blood vessels, or endothelial cells. Previous studies have shown that MCR1 activation increases melanin production but limits inflammation. Melanin is a natural pigment that produces pigmentation in hair, eyes, and skin.

MT-7117, also known as dersimelagon phosphoric acid, is an oral medication that activates the MC1R. It has been shown to make monkeys’ skin darker, but whether it can be an effective treatment for SSC is unknown.

A research team that included scientists at Mitsubishi Tanabe Pharma investigated the effect of MT-7117 on lung inflammation, skin scarring, and vascular impairment in a rat model of SSc. They also evaluated the effect of MT-7117 on the activation of skin cells called fibroblasts and compared the presence of MCR1 in skin biopsies from healthy donors and those with SSc.

SSC-like disease was induced by injecting bleomycin, a chemical that treats cancer but also causes scarring and inflammation in mice. In the first set of experiments, researchers gave mice MT-7117 orally and high-dose bleomycin daily for about a month. As expected, high-dose bleomycin caused weight loss, skin scarring, lung injury, and pneumonitis. Co-administration of MT-7117 inhibited skin scarring and lung inflammation in a dose-dependent manner, while significantly improving body weight.

In another experiment, skin fibrosis was gradually induced over a six-week period, with mice receiving bleomycin every day for six weeks. MT-7117 was started three weeks after bleomycin administration and significantly inhibited bleomycin-induced skin thickening, and attenuated the loss of skin white adipose tissue.

Using human fibroblasts, the scientists found that MT-7117 reduces fibrosis by preventing fibroblast activation through transforming growth factor (TGF)-beta, a protein known to promote fibrotic processes.

“The suppression of human fibroblast activation by MT-7117 is an important finding, demonstrating that MT-7117 exerts its anti-fibrotic effect by directly targeting fibroblasts and that it acts not only in animal models but also on human fibroblasts,” the researchers wrote.

MCR1 expression was similar in skin biopsies of healthy donors and people with SSc, regardless of scleroderma type. The protein is found primarily in immune cells called monocytes and macrophages, but it is also present in fibroblasts, endothelial cells, and neutrophils.

The scientists found that MT-7117 reduces inflammation and fibrosis, primarily by decreasing inflammatory cell activation and production of the pro-inflammatory molecule interleukin-6.

“There was also evidence that MT-7117 limits vascular dysfunction by acting on endothelial cells. Furthermore, MT-7117 showed an anti-fibrotic effect by suppressing fibroblast activation,” the researchers wrote. “Due to its strong beneficial effect on all three underlying diseases of SSc, MT-7117 is a potential therapeutic agent for the treatment of clinically difficult SSc, which is characterized by diverse symptoms and difficult to treat.”