A monoclonal antibody-based drug called SYN0012 is currently being investigated in human clinical trials for the treatment of rheumatoid arthritis, an autoimmune disease. However, the anti-inflammatory activity of this drug may also lead to it being a treatment for aortic valve stenosis, the first of its kind.
Aortic valve stenosis is a disease of the heart valve that allow blood to pass through to the body’s vessels for delivering oxygen and nutrients to tissues. This disease is characterized by valve calcification, or hardening, from excess fibroblast-produced cadherin-11, a binding protein. Abnormally high levels of cadherin-11 leads to stiffening of the heart valve, causing the heart to work harder to pump the same amount of blood to the vessels. Making the heart work too hard can lead to heart failure, and as soon as symptoms begin, heart failure and death become risks.
Now, Vanderbilt University scientists are interested in SYN0012 as a technique to maintain a normal, healthy level of fibroblasts and cadherin-11. The antibody works by binding cadherin-11, a protein which in normal contexts promotes healthy wound healing.
"We believe there is potential for using this drug at the first sign of valve disease to prevent the progression,” said associate professor W. David Merryman from Vanderbilt. “You likely cannot reverse the damage, but we believe the drug can prevent it."
The current treatment approach for aortic valve stenosis is surgical replacement, a dangerous option, especially for older patients. SYN0012 could provide an alternative solution.
How did scientists realize that an anti-inflammatory drug for treating rheumatoid arthritis would work similarly in the context of heart valve calcification? A 2013 Vanderbilt study of heart valve cellular responses, focusing on one specific chemical compound, resulted in two different outcomes.
One graduate student on the project identified the compound as exacerbating valve disease, and the other saw the compound as preventing disease. This anomale led to the discovery of cadherin-11 production and its influence on the progression of valve disease. In further studies, heart valves from patients who had underwent a surgical procedure to replace their valves due to disease had nearly 50 times greater cadherin-11 levels than healthy valves.
"The exciting thing about this drug's potential is that it could allow us to consider a strategy of prevention, as we do with other forms of heart disease, like lowering cholesterol or using ACE inhibitors, explained Vanderbilt cardiologist Mike Baker. “We don't have any interventions for aortic valve stenosis that slow its progression."
The present study was published in the journal Circulation.
Source: Vanderbilt University
