A search is on for an anti-inflammatory treatment targeting the C-reactive protein — CRP, a biomarker of inflammation produced by the liver — of possible use in a wide variety of conditions, including immune-mediated diseases such as multiple sclerosis (MS).
Researchers at the Baker Heart and Diabetes Institute and the University of Melbourne, both in Australia, are working to find compounds that target CRP and may ease the inflammatory reaction its overproduction can provoke.
“An overshooting of the body’s inflammatory response causes some of Australia’s most common and debilitating health conditions, including atherosclerosis — the inflammation of arteries that can lead to heart attack and stroke — sepsis, multiple sclerosis, arthritis, and viral infections such as COVID-19,” Karlheinz Peter, MD, PhD, a cardiologist and deputy director at the Baker Institute, said in an institute press release.
The research team has been studying the 3D structure of CRP using techniques such as X-ray crystallography to better understand the protein’s structure and inflammatory function.
This insight is expected to aid in finding and developing treatment candidates using a computer simulation program. Through a virtual library, scientists will search thousands of compounds already available for human use. Each compound identified will be bound to the CRP structure via the computer program, with the most promising ones then being tested as treatment candidates.
“Ultimately we want to find which of these drug compounds will fit most tightly into the C-reactive protein’s pockets [regions in its structure] and by doing so inhibit inflammation,” said Michael Parker, PhD, a structural biologist and director of Bio21 Institute at University of Melbourne.
“We already have some pilot data to narrow down the families of drug-like compounds that may work best. But they need optimization to find the specific drug that will block the C-reactive protein most effectively, so patients only need to take the smallest dose,” Parker added.
Previous studies on rats given a limb transplant showed that some identified compounds minimized the effects of inflammation, extending the animals’ life.
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