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Growth Hormone May Be Tied to Three Deaths

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Times Medical Writer

An infectious agent that is suspected of causing several rare and fatal brain diseases may be implicated in the deaths of three adults who were treated as youngsters with human growth hormone, a substance derived from the brain tissue of cadavers.

Known as a prion, the suspect agent is believed to be the cause of Creutzfeldt-Jakob disease, a degenerative brain disorder. Prions were first identified by Dr. Stanley B. Prusiner, a University of California, San Francisco, neurologist whose decade of research indicates that they may be unique among all known infectious agents, in that they contain no genetic material.

Over the weekend, the federal government ordered a halt to the distribution of human growth hormone to about 150 physicians in the United States who use it to treat growth-deficient children. Human growth hormone is extracted from cadaver pituitaries, a gland that is a part of the brain.

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The order was issued after three deaths that have occurred since last November in individuals who were treated with the hormone prior to 1977. One of the three deaths has been confirmed as due to Creutzfeldt-Jakob. The other two are also suspected to be Creutzfeldt-Jakob cases but have yet to be confirmed.

If the victims developed their diseases as a consequence of being treated with a growth hormone contaminated by the agent responsible for Creutzfeldt-Jakob, scientists assume that it came from a pituitary donor who was infected with the agent.

Dr. Mortimer B. Lipsett, director of the National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases, said the intent of the government order is to temporarily discontinue distribution of the hormone until assurance of its quality has been determined.

In a telephone interview from Bethesda, Md., Lipsett said a delay of up to 18 months will be necessary in order to see whether the hormone contains viruses, prions or any other infectious agent that can attack nerve cells. This will be done by injecting experimental animals with the hormone to see whether disorders similar to Creutzfeldt-Jakob develop.

According to Dr. Albert F. Parlow, a research professor at UCLA Medical School whose laboratory at Harbor-UCLA Medical Center in Torrance is the only one in the country that processes the pituitaries used to make the growth hormone, such tests have not been routinely conducted in the past.

Parlow said, “It is not technically feasible to detect either prions or so-called ‘slow viruses’ in growth hormone,” except by the animal experimentation method. Some viruses are called slow viruses, because of the length of time that elapses before symptoms appear.

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“Detecting the presence of (slow) virus contamination is a long, cumbersome and difficult procedure,” he said.

Parlow read from a letter from Lipsett declaring that “the weight of evidence suggests there is no contamination of current human growth hormone.” Nevertheless, according to Lipsett, distribution of the hormone is being held up as a safety precaution.

Scientists cannot say for sure that prions were the cause of the three deaths. For one thing, there has been much skepticism that it is possible for an infectious agent to not possess genetic material.

On Monday, however, Prusiner, Dr. Leroy E. Hood of Caltech and researchers for the University of Zurich released a report detailing how prions may be able to reproduce in sufficient numbers to infect the brain, despite the lack of genetic material.

Exact Copies

Their work indicates that during infection, the prion reproduces itself by altering a natural protein in the body in such a way as to create exact copies of itself. The prions then accumulate in the brain and lead to the symptoms of the disease.

Previous studies have shown that prions aggregate into rods and filaments similar to those found in the brains of Creutzfeldt-Jakob disease. The configurations also resemble the plaques found in the brains of people with Alzheimer’s disease.

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