Mizzou researchers explore first drug treatment for aortic valve calcification

University of Missouri researchers are advancing a promising new approach to treating a serious heart condition that affects millions of older adults worldwide.

Dunpeng Cai, an assistant professor in the School of Medicine, has received a five-year, $2.8 million National Institutes of Health R01 grant - one of the agency's most competitive and prestigious awards - to uncover what causes aortic valve calcification. The progressive disease causes the heart's aortic valve to harden and narrow over time, forcing the heart to work harder and leading to chest pain, shortness of breath and heart failure.

Now, Cai is investigating what could become the first drug treatment for the disease.

The mechanisms driving aortic valve calcification are extremely complex, making the disease difficult to study. Millions of patients are waiting for a treatment, and that makes this challenge worth pursuing."

Dunpeng Cai, assistant professor, School of Medicine, University of Missouri

Working with clinicians at University Hospital, Cai previously compared healthy tissue and calcified human aortic valve tissue. At the time, he discovered that patients with aortic valve calcification have higher levels of DOCK2, a protein involved in regulating immune cells, within the cells of the aortic valve.

The new grant will allow his team to test whether blocking DOCK2 with a drug can slow or prevent the disease.

"If we can show that knocking out DOCK2 with a drug compound in animal models can slow, stop or even reverse the buildup of calcium in the aortic valve, the drug may also work in humans with the disease," Cai said. "What's important to remember is that most proteins can have both a good side and a bad side. Since DOCK2 plays a key role in the immune system, the goal is to target its role in aortic valve calcification without causing unwanted side effects."

As part of the grant, Cai's team will study aortic valve cells in the lab to better understand the role DOCK2 may play in driving the disease.

If the approach proves successful, Cai plans to collaborate with researchers at the Roy Blunt NextGen Precision Health building to advance a promising drug compound into clinical trials. NextGen Precision Health, along with the Genomics Technology Core in the Bond Life Sciences Center, helps accelerate these types of discoveries, he said.

"At some universities, researchers have to seek out these resources externally," Cai said. "Having world-class research infrastructure right on campus here at Mizzou helps us conduct our research much more efficiently."