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Scripps Team Develops Promising Lung Drug - Medicine: Artificial surfactant is hailed as breakthrough in keeping premature babies alive.

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NORA ZAMICHOW, TIMES STAFF WRITER

Scientists at Scripps Research Institute have developed an artificial lung substance that in animal tests prevented respiratory distress syndrome, a major killer of premature babies, according to a study published today.

Researchers have tried for years to develop a synthetic form of the substance, called surfactant. Each year, about 39,000 premature babies are born without surfactant and develop respiratory distress syndrome, an inability to keep the lungs’ air sacs open. The disorder also affects about 150,000 adults a year.

In healthy people, surfactant is secreted by lung cells, coating the inner lining of the lung and preventing it from collapsing when a person exhales. Several other artificial versions have been developed in attempts to prevent the syndrome, but with varying success.

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Scientists hope that the latest synthetic version developed at Scripps will prove the most effective yet, acting most like the real human substance it mimics.

“This may come as close as you are going to get without actually being human surfactant--this may well be the best,” said Dr. Louis Gluck, a professor of pediatrics and director of newborn medicine at UC Irvine.

Pending federal approval, the new drug will be tested on premature babies early next year, said Dr. Charles Cochrane of Scripps’ immunology department and an author of the study, published in the journal Science.

The drug, which is administered to the lungs through a tube in the trachea, has been tested on 18 prematurely delivered rhesus monkeys and scores of rabbits, and is “just far more effective than anything we have,” Cochrane said.

The monkeys, who were born 80% mature, were gray and ashen, laboring to breathe until they were given the drug, the Scripps doctors said. Within six hours, they became pink and were breathing easily.

Respiratory distress syndrome kills a quarter of the infants and about half the adults it strikes, according to the American Lung Assn. The adult victims’ lungs become inflamed and stop producing surfactant.

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Just before birth, babies develop the ability to produce surfactant, which is composed of proteins and fatty substances called lipids. But those born prematurely frequently cannot produce the substance and are unable to expand their lungs. This means they receive too little oxygen and cannot empty the carbon dioxide from their lungs.

These infants are dubbed “$100,000 babies” because of the costs associated with placing them on respirators and keeping them alive, Cochrane said. The respirators--in some cases combined with the administration of existing surfactants--maintain the infants until their lungs are mature enough to function on their own.

The new synthetic surfactant is inexpensive to produce and could significantly reduce the cost of treatment by preventing the babies from developing what can be devastating lung ailments, Cochrane said.

“You are dealing with babies who are terribly sick,” he said. “These people are dying, and you’ve just got to do something for them.”

Artificial surfactants have been available only in recent years. In 1963, Patrick Bouvier Kennedy, the 2-day-old son of then-President and Mrs. John F. Kennedy, died of the disorder.

One now-available surfactant is made from cow lungs, but some humans develop harmful allergic reactions to it. And, because it takes five cow lungs to produce one dose, that treatment is also expensive, said Susan Revak of Scripps’ immunology department and another author of the study.

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Cochrane and Revak also worked with Dr. T. Allen Merritt of UC Davis, Dr. Gregory Heldt of UC San Diego and Dr. Mikko Hallman of UC Irvine.

The research has proven valuable, Heldt said, not only because the team was able to develop the new surfactant, but also because, for the first time, experts now understand the role of proteins in natural surfactant.

“It’s a very significant breakthrough,” he said.

One existing synthetic surfactant, Exosurf, lacks proteins--a factor that scientists believe may make it less effective than the new one developed at Scripps, Cochrane said.

During his and Revak’s four years spent studying surfactants, they discovered that one protein, called Surfactant Protein-B, played a key role in keeping air sacs open in the lungs. Next, the Scripps team set to work creating a synthetic version of the components of surfactant, including the protein.

“The protein holds everything together like reinforcing concrete with steel . . . “ Cochrane said. “Protein is very important to surfactant functioning because it forms stability among the lipid layer, providing strength to keep the air sacs open.”

Other experts voiced cautious optimism and agreed that the protein could make the drug a more effective treatment.

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“It certainly would be considered by most of us as a real advantage that should help improve babies--it probably would be something with advantages over what we now have,” said Dr. Ron Ariagno, a professor of pediatrics at Stanford University.

Clinical trials of the drug are set to begin in early 1992, Cochrane said.

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