A research team at the University of Miami Miller School of Medicine has shown that a small protein called melanocyte-stimulating hormone (a-MSH) reduces the inflammation associated with sarcoidosis.
In the process, the team also developed an improved research model to better understand the disease and study additional therapies. Their research was published in the journal Scientific Reports.
Sarcoidosis is a painful, sometimes fatal, condition caused by inflammatory nodules called granulomas. A chronic disease, sarcoidosis can affect the lungs, skin, liver and other organs, causing fatigue, weight loss and joint pain. Though it’s believed the disease is caused by environmental factors, sarcoidosis is poorly understood and has few treatments.
“We don’t have any specific therapies for sarcoidosis,” said Mehdi Mirsaeidi, M.D., M.P.H., associate professor in the Department of Medicine’s Division of Pulmonary, Critical Care, Sleep and Allergy, director of the University of Miami and U.S. Department of Veterans Affairs’ sarcoidosis programs, and leader of the research team. “We are limited to steroids, such as prednisone and prednisolone, but patients who use steroids for a while are going to have a lot of side effects.”
To help give patients better choices, Dr. Mirsaeidi and colleagues needed new tools to study the disease. The first step was creating an improved granuloma model. The group used cell wall microparticles from a microbe called Mycobacterium abscessus to challenge peripheral blood cells from sarcoidosis patients.
“We know there is something in the environment that stimulates this kind of inflammation,” Dr. Mirsaeidi said. “From that knowledge, we developed a model based on a very common environmental bacterium.”
This process created well-defined granulomas that closely resembled those found in patients — a model that will be quite useful for studying how granulomas form, delineating different forms of sarcoidosis, and testing potential diagnostics and treatments.
Having created the new disease model, the researchers used it to test a-MSH, a common peptide (piece of a protein) in the body with known anti-inflammatory capabilities. They found a-MSH reduced inflammation in the granuloma model by modulating CREB, a protein that regulates several genes, including a group of inflammatory cytokine proteins called interleukins. This was the first time a-MSH had been shown to reduce granuloma-caused inflammation.
The group believes a-MSH has great potential to help sarcoidosis patients and will continue their work in animal models and, eventually, patients. In addition, they will leverage the new granuloma model to look for other potential treatments.