Arthritis Drug Could Potentially Treat Severe Heart Condition

A drug designed for rheumatoid arthritis might be able to cure a severe heart condition, finds a study from Vanderbilt University. The research study was published in Circulation, the journal of the American Heart Association.

The research team published the findings that a new drug - monoclonal antibody known as SYN0012 may show promise in keeping the heart valve leaflets supple.

Around one-fourth of the Americans, has been found to suffer from the hardening of the valves by the age of 65. And around half of them by the age of 85.

Surgical replacement of the valves is the only treatment. Cyndi Clark, research assistant professor of biomedical engineering, said, "Very elderly patients’ bodies can’t handle that."

"I hope to see an earlier treatment option available within the next decade."

Rheumatoid Arthritis Drug
The rheumatoid arthritis drug is an anti-inflammatory agent, that is capable of binding to cadherin-11 (CDH-11) on the surface of the cells so that they cannot bind together.

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W. David Merryman, associate professor of biomedical engineering, said, "Aortic valve stenosis, even though it involves only a little piece of tissue, has a catastrophic effect on the heart."

"The antibody we’re working with blocks fibroblasts from becoming the active type that leads to disease. It keeps them from becoming inflamed.”

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"We believe there is potential for using this drug at the first sign of valve disease to prevent the progression. You likely cannot reverse the damage, but we believe the drug can prevent it."

The surgeons can replace the damaged valves with ones that are made with pig or cow tissue along with mechanical versions. However, the only option for the physicians is to monitor the calcifying valves when they are detected and then could be operated when the symptoms appear.

Baker said, "Once the patient becomes symptomatic, they start running a significant risk of heart failure or even death."

"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. We don’t have any interventions for aortic valve stenosis that slow its progression."

Potential Cure
The research on CDH-11 may date back to 2013 when two Ph.D students compared the two studies of heart valve cellular responses that has come to completely different conclusions.

One of the studies found that a chemical compound caused valve fibroblasts that can become active and could be similar to what is observed during valve disease.

However, the other study indicated that the same compound prevented the cells from calcifying, indicating that a key piece of the valve disease was missing.

The research team realized that the teams behind those studies turning CDH-11 production on and off, that could affect the outcome.

The heart valves that were preserved from surgeries at Vanderbilt University Medical Center and found that patients suffering from calcification. However, in some cases, 50 times such as CDH-11 present in the valves as patients without the condition.

The study showed a NOTCH1 genetic mutation may likely ensure that carrying it eventually would suffer from heart valve disease as it could lead to CDH-11 overproduction.

Heart Valve Calcification
The aorta is the main artery that carries the blood from the heart to the rest of the body. Aortic valve calcification occurs because of calcium deposits on the aortic valve in the heart. In aortic stenosis, the aortic valve may not open fully and could decrease the blood flow to the heart.

The culprit is cadherin-11, a binding protein that is necessary for normal wound healing. Fibroblasts are present in the connective tissue and heart valves are composed of this type of cell.

As the heart age and loses elasticity, the fibroblasts could become overactive and produces more amount of the binding cadherin-11 protein until the leaflets that make the aortic valve immobile.

The heart might pump harder in an attempt to push the blood through the valve, by causing the heart chambers to enlarge and could lead to heart failure if the valve is not replaced.

References

1. Cynthia R. Clark, Meghan A. Bowler, J. Caleb Snider, W. David Merryman. Targeting Cadherin-11 Prevents Notch1-Mediated Calcific Aortic Valve Disease. Circulation, 2017; 135 (24): 2448 DOI: 10.1161/CIRCULATIONAHA.117.027771
2. Aortic stenosis - ( https://medlineplus.gov/ency/article/000178.htm)

Source-Medindia