Drug treats thick heart muscles in mice

People with hypertrophic cardiomyopathy have an increased risk of sudden cardiac death. "If we could develop an effective treatment for the disease and improve patients' heart function, we could save many people's lives," says Maike Krenz. (Credit: Duane Schoon/Flickr)

A drug compound appears to reduce the thickness of heart muscles in mice that have a form of congenital heart disease known as hypertrophic cardiomyopathy.

Congenital heart disease is the most common form of birth defect, affecting one out of every 125 babies, according to the National Institutes of Health.

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By suppressing a faulty protein, researchers were able to improve the mice’s cardiac functioning, says Maike Krenz, assistant professor of medical pharmacology and physiology at the University of Missouri School of Medicine.

In 2001, researchers discovered a gene that linked hypertrophic cardiomyopathy to the genetic conditions Noonan syndrome and LEOPARD syndrome. In Noonan and LEOPARD syndromes, the thickened heart muscle of hypertrophic cardiomyopathy is caused by a defective Shp2 protein, created by a mutation in the gene PTPN11.

“Previously, not much has been known about the biochemistry behind Shp2 and hypertrophic cardiomyopathy,” Krenz says. “We know the thickened heart muscle is sick and doesn’t work properly, and we know a defective Shp2 protein can cause heart muscle to thicken. However, to create an effective treatment, we need to know what Shp2 is doing inside the heart to cause the defect.”

To test whether they could interrupt the heart’s hypersensitivity to growth signals, researchers gave a chemical compound, PHPS1, to mice with a mutated gene that produces the defective Shp2 protein.

“Not only did the compound reduce the thickness of the heart muscle to the size of normal heart muscle, but it also improved the cardiac pumping of the heart,” Krenz says.

“That’s important because people with hypertrophic cardiomyopathy have an increased risk of sudden cardiac death. If we could develop an effective treatment for the disease and improve patients’ heart function, we could save many people’s lives.”

Because of the role Shp2 plays in signaling heart growth, Krenz believes the research could be translated in the future into improved treatments for other types of heart disease, such as damage caused by heart attack.

Krenz presented the research findings late last year at the American Heart Association’s Scientific Sessions conference.

Source: University of Missouri