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New drug may fight deadly heart rhythm

A new drug may help prevent deadly heart rhythms that kill hundreds of thousands of people every year, researchers reported Thursday.
/ Source: Reuters

A new approach to treating heart failure could prevent the irregular heart rhythms that kill hundreds of thousands of people every year, U.S. researchers reported Thursday.

They found a leaky cellular channel causes the deadly heartbeat patterns, or arrhythmias, and found a drug that seems to plug the leak without causing serious side-effects.

The drug has only been tested in mice. But the researchers at Columbia University in New York say some people with a genetic predisposition to develop fatal arrhythmias while exercising have the same defective channel.

It suggests that what works in mice might work in people, said Dr. Andrew Marks, a cardiologist and molecular biologist who led the study.

“About four years ago we found a calcium channel that was defective in patients with heart failure,” Marks, head of the physiology department at Columbia, said in a telephone interview.

While some heart drugs are called calcium channel blockers, this channel, involved in muscular contractions, was actually a different molecular doorway, Marks said.

“It is not able to close tightly, so it becomes leaky,” Marks said. “Patients with mutations in the channel that cause sudden cardiac death also have this leak. We decided if we could come up with a drug that could plug up the leak we’d have a treatment for heart failure.”

An estimated 5 million Americans have heart failure, a chronic condition caused by the heart’s inability to pump blood properly. It can be caused by a virus, by a heart attack, or by chronic high blood pressure, and kills half of its victims within five years.

The irregular heart rhythm caused by heart failure kills 340,000 Americans each year, according to the American Heart Association.

No cure available
There is no cure for heart failure and patients must take cocktails of drugs. Many can only survive with a heart transplant or with an implanted device that keeps the heart beating properly.

But a drug that targets the molecular cause could be taken as a pill.

“We know exactly what is causing the leak,” Marks said.

A protein called calstabin2 attaches to calcium channels and closes them. They found a drug called JTV519 helps calstabin2 stop the leak.

“It does that without blocking the channel, so we are not inhibiting the natural function of the channel, which opens to make muscles contract,” Marks said.

Other channel blockers totally shut off the channels they target, sometimes causing toxic side-effects. Many have been pulled out of development because they caused worse problems than they solved, Marks said.

Writing in the journal Science, Marks and colleagues said the drug completely prevents sudden death from arrhythmia in mice that have the same heart defect as people with heart failure.

“The drug will be an incredible advance if it works in patients,” Marks said in a statement.

“It represents the beginning of an era when drugs will directly fix the molecular defects in heart failure. While our drug is one of the first molecular-based therapies for heart failure and arrhythmias, it won’t be the last.”

He said his team was now looking for a drug company to help them make the drug and test it.

“We are moving ahead very quickly to develop it for clinical (human) use,” Marks said.

“Our idea is to take a pill instead of spending hundreds of thousands of dollars on implants and heart transplants.”