New drug approach may fight lethal heart rhythm

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New drug approach may fight lethal heart rhythm

Last Updated: 2004-04-08 15:29:00 -0400 (Reuters Health)

WASHINGTON (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 on Thursday.

They have identified a drug that seems to plug the leaky cellular

channel that causes the deadly heartbeat patterns, or arrhythmias, and

does not cause serious side effects.

The drug has only been tested in mice, but researchers at Columbia

University in New York say some people with a genetic predisposition to

develop fatal arrhythmias while exercising have the same defective

cellular channel.

The findings suggest that what works in mice might work in people, said

Dr. 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.

There is no cure for heart failure and patients must take a combination

of drugs. Many patients 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 is 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

(human) use, " Marks said.

" Our idea is to take a pill instead of spending hundreds of thousands of

dollars on implants and heart transplants. "

SOURCE: Science, April 9, 2004.

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org