UConn Health is trying to save lives with stroke research. An ‘entirely different approach’ might be the answer.

Researchers from UConn Health are investigating a new way to treat stroke that focuses on reducing inflammation caused by the attack and limiting the damage to the brain.

“For 20-plus years now, there has not been any new medical therapy to treat patients with stroke,” said Dr. Bruce Liang, a cardiovascular clinical scientists and one of two UConn authors of a new study in the Journal of Medicinal Chemistry.

“What we have uncovered is an entirely different approach to develop a new medicine to treat stroke, which has this huge unmet medical need because there’s been no new medicine for so long, and patients with stroke still suffer,” Liang said. “And it’s the leading cause of disability in the country.”

According to the American Stroke Association, stroke is the fifth-leading cause of death in the United States and a leading cause of disability.

The traditional method is to dissolve the clot that has blocked blood flow to the brain or to repair a ruptured artery. “Our medical approach is to treat the inflammation associated with the stroke,” Liang said.

“So after the patient develops a stroke there is a huge amount of inflammation in the brain, which causes damage,” he said. “So if we could block that inflammation with this new medicine, we could decrease the size of the stroke. And we know if you decrease the size of the stroke, patients will do better.”

Besides stopping inflammation, “you also help resolve it, so that the brain has a better chance of recovering,” Liang said.

“What happens is, during the stroke, a lot of cell death occurs immediately,” said Dr. Rajkumar Verma, a neuroscientist at UConn Health. Those cells release a molecule known as ATP, for adenosine triphosphate.

When the cell dies, “it just spills over everything that it has inside,” Verma said. And the released ATP binds to neighboring cells’ energy receptors, called P2X4, he said, leading to an influx of the calcium ions that damage the brain cells.

The result is the spread of inflammation in the neighboring cells, “so this is like a cascade of events,” he said.

P2X4 is what the new compound targets.

“When ATP is too much, it leads to too much influx of the calcium,” Verma said. “A normal amount of calcium is required for normal activity of the cells. But if it is too much, it will activate the cellular system, which activates several enzymes.” One of those enzymes leads to release of cytokines, which cause the inflammation.

“So this compound … blocks these receptors, so that ATP doesn’t work on it,” Verma said. “The extra ATP, which is released from the dying cell, will not be able to activate the neighboring cells,” stopping the spread of the damage to those cells, he said.

The drug being studied is “a new chemical entity,” Liang said. “It’s small [molecules] so we can get to the brain of the stroke subjects and block the inflammation and help resolve the inflammation.”

So far, the molecule, known as MRS4719, has been tested in animals. The next step is a safety study in animals, Liang said.

“This is at the early stage; a lot more work is needed,” he said. “But because it’s different and novel, we think right now it’s piqued the interest of the scientific community.”

Ed Stannard can be reached at estannard@courant.com.