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Chemical-Armed Antibodies May Be New Heart Attack Weapon

August 15, 1985

BOSTON (AP) _ Scientists have bonded special antibodies to a powerful clot-dissolving chemical and say they may be able to stop heart attacks without touching off dangerous bleeding throughout the body.

The researchers say their development could represent a new, safer way to deliver potentially life-saving drugs to heart attack victims.

Usually, a heart attack occurs when a blood clot blocks one of the arteries that feed the heart. Unless the clot breaks up, a section of the heart muscle is starved of oxygen and dies.

Now, researchers at Massachusetts General Hospital have created an antibody that zeroes in on fibrin, one of the components of blood clots. And it carries with it urokinase, a natural, clot-dissolving enzyme.

So far, the scientists have experimented with their newly created material in the test tube but not in animals or people. However, they say that if all goes well, human testing could begin within two years.

Doctors at Johns Hopkins this week reported using a similar strategy to treat advanced liver cancer. They joined antibodies with radioactive isotopes. The antibodies sought out cancer tissue and attacked them with radioactivity.

In the past, doctors have widely used two clot-dissolving substances, urokinase and streptokinase, in an effort to stop heart attacks before they cause permanent damage. Typically, the chemicals are injected into the body or delivered to the heart through a tube.

However, this approach has a major drawback. The urokinase and streptokinase will also activate plasminogen, a clot-dissolving material in the blood. As a result, the blood fails to clot properly throughout the body, and uncontrollable, possibly lethal bleeding may occur.

Delivering the urokinase with antibodies appears to circumvent this hazard. The enzyme would be shuttled directly to the fibrin in the clot, not to the plasminogen in the blood. As a result, the clot is dissolved but the plasminogen is spared.

The researchers found that in the test tube, at least, the urokinase carried by antibodies was 100 times more powerful at lysing, or dissolving, clots than was urokinase alone.

Dr. Gary R. Matsueda, one of the researchers, said the new approach should dissolve clots faster and more completely, as well as more safely, than urokinase or streptokinase administered by themselves.

″My bet is that getting a very high concentration (of urokinase to the clot) would do more for complete lysis than anything,″ he said.

The latest work opens up many possibilities for engineering new therapies for heart attack victims, said Dr. Christoph Bode, who directed the study, which was published in the latest issue of the journal Science.

″Urokinase is just an example of what we can try,″ he said. ″We will eventually couple other agents and see if the action can be enhanced. The concept is new. We can play all sorts of games by trying different agents and different antibodies.″

The antibodies used in the experiments are called monoclonal antibodies. Antibodies are chemical weapons in the blood that ordinarily attack germs and other foreign invaders, and the body produces a vast assortment of them. In recent years, however, scientists have learned to manufacture pure, identical antibodies that will seek out anything in the body that their creators wish to find, including parts of the body itself.

Others contributing to the study were Drs. Kwan Y. Hui and Edgar Haber.

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