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Groundbreaking model of heart disease rewarded with NIH Pioneer Award

Submitted by on 26 December, 2020 – 4:32 pm
A model pioneered by the University of Utah, the cardiologist suggested as a cause of heart disease is the kind of creative thinking from the National Institutes of Health (NIH) likes to see-and benefits with one of his greatest honors, a grant of 2.5 million U.S. dollars 2009 Pioneer.

Ivor J. Benjamin, MD, professor of internal medicine and biochemistry and the Christi T. Smith Cardiovascular Research Chair at U of U School of Medicine, believes that one of the most powerful antioxidants in the body, molecules widely believed to protect the heart may actually lead to heart disease and other organs, when a genetic mutation causes the body to produce an excess of the molecule. His theory, which aroused some controversy when Benjamin presented in a 2007 study in the journal Cell, represents a paradigm shift in understanding the causes of heart disease. But with the conviction that new and unconventional ideas to boost science forward, and after a very competitive process and critical review, the NIH chose Benjamin to further investigate the idea as one of 18 researchers to receiving a Pioneer Award.

NIH Director, Francis Collins, MD, Ph.D., will present Benjamin and the other recipients of their awards at a ceremony this Thursday, September 24th at the headquarters of the agency in Bethesda, Maryland Benjamin will receive $ 500,000 per year over five years to continue his research. Much of the resources of the Pioneer Award program is that it encourages researchers to think outside the box while receiving substantial funds to test their ideas, according to Collins.

“The fact that we kept getting so strong proposals for funding through the test program of the wealth of creative ideas in many fields of science today,” he said.

The Pioneer Awards are part of a beer than 115 grants to promote innovative medical research and potentially transformative. The NIH awarded a total of $ 13.5 million to Pioneer this year’s award winners.

An estimated 3 million Americans suffer from heart failure, with 500,000 new cases diagnosed annually. Disease that leads to heart failure has long been associated with oxidative stress, a process in which the body produces “free radicals”, molecules in response to the intake of oxygen. Once they are produced, free radicals roam the body, creating chemical reactions that damage organs and other tissues.

To protect cells from free radical, the body produces antioxidants. Benjamin work focuses in particular, an antioxidant, reduced glutathione, which occurs when a protein called alpha B-crystalline develops inside the cells. When mutated version of the human gene that makes alpha B-crystalline were placed in mice, however, certain metabolic pathways are activated inappropriately, leading to excessive production of reduced glutathione and heart in animals. Benjamin terms this condition “reductive stress.”

Until recently, reductive stress has not been looked at in the context of the disease. But Benjamin showed that mice with reduced glutathione too had increased rates of heart failure, while those with normal levels of antioxidants did not develop heart failure. Given the role of antioxidants, the theory is counterintuitive, Benjamin admits. But if correct, could lead to development of an entirely new class of “antireductant” drugs to treat or even prevent heart disease caused by stress reduction. “Our findings show that the reducing potential stress that causes heart disease definitely deserves more research,” says Benjamin. “The Pioneer Award will allow us the freedom to investigate the consequences and mechanisms of reducing stress and, hopefully, make the kind of work that can be transformative.”

Benjamin’s research represents the kind of imagination and the pursuit of science that the U of U values in its faculty, according to Lorris Betz, MD, Ph.D., University of Utah, vice president of health sciences . “As a research university, we want our researchers to extend the boundaries of science, even when it means to question or contradict conventional theories and wisdom,” says Betz. “Ivor Benjamin does just that. On behalf of the entire University of Utah Health Sciences community, I congratulate and applaud Dr. Benjamin to be recognized with this great honor.”

Although the Pioneer Award is in its name, Benjamin is quick to credit his team of laboratory and colleagues with making the award possible. “I am honored and humbled to be chosen for the award,” he says. “But the real story is my multidisciplinary team. They deserve much credit, too.”

Source: University of Utah Health Sciences (web)

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