Compounds Targeting Inflammatory C-reactive Protein Under Study in Australia

Compounds Targeting Inflammatory C-reactive Protein Under Study in Australia
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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.

According to the team, anti-inflammatory compounds targeting CRP could potentially “also reduce the amount of muscle lost in a heart attack, address the inflammation of joints that causes arthritis, and potentially reduce the progression of multiple sclerosis and other diseases where the immune system is overacting and fighting against the body,” Parker said.

Viral infections such as COVID-19 might also benefit from this work, the researchers said.

“When you have any sort of virus, the liver produces lots of this C-reactive protein, sometimes leading to a 1000-fold increase in the body. And we’ve seen with COVID-19 patients, when this protein marker is raised your chance of dying is sky high,” Parker said.

However, they stressed that any promising treatment coming from this work will take several more years to develop to the point of commercial use.

“While the ultimate aim of our project is to have a drug on the market, drug development is costly and a lengthy process to ensure efficacy and safety in human patients,” Parker said.

This project is supported by AU$200,000 (almost $145,000) in seed funding from the Baker Department of Cardiometabolic Health at the university’s medical school.

“We expect that by continuing this significant collaboration, and by elevating that work through the new Baker Department of Cardiometabolic Health at the Melbourne Medical School, we will attract the further funding we need to get a highly promising drug to market,” Parker added.

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Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.

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