Pregnancy protein looks promising in AIDS fight Mystery agent found to boost bone marrow

March 31, 1998|By Jonathan Bor | Jonathan Bor,SUN STAFF

A natural substance produced by women in the first trimester of pregnancy might have broad uses in the fight against AIDS and cancer, Dr. Robert C. Gallo said yesterday.

Gallo, writing in today's issue of Nature Medicine, said the substance appears to suppress the AIDS virus and promote the growth of bone marrow, the body's factory for infection-fighting blood cells. Earlier studies showed that the substance shrank tumors caused by Kaposi's sarcoma, a painful and disfiguring cancer that strikes many AIDS patients.

Gallo, who leads the University of Maryland's Institute of Human Virology, emphasized that years of research will be needed to establish the protein's therapeutic value. But he and others familiar with the work say the most exciting feature might be its potential to boost bone marrow.

In theory, the substance could help to protect patients from the side effects of chemotherapy and other cancer treatments that sicken patients by destroying bone marrow. In this way, it could allow patients to tolerate more treatment than is now possible.

"The thought is, you could help people who have suppression of bone marrow from some causes, maybe not all causes," Gallo said.

Although supervised by Gallo, the research was chiefly conducted by Dr. Yanto Lunardi-Iskandar and Dr. Joseph Bryant of the virology institute, along with Dr. Steven Birken of Columbia University.

Two years ago, Gallo's team announced that the compound was surprisingly effective in treating, although not curing, Kaposi's sarcoma in laboratory mice and in some AIDS patients treated at clinics in California and Belgium. At the time, they believed the active substance was a hormone -- human chorionic gonadotropin (hCG) -- that is produced by the placenta during pregnancy.

The hormone is commercially extracted from the urine of pregnant women to treat hormonal conditions in men and women.

Recent experiments have shown that the compound effective against Kaposi's is not hCG but another protein that is also present in the urine of pregnant women. Gallo said the compound is either a fragment that results from the natural breakdown of hCG or a different substance.

"My one disappointment is that we haven't identified it yet," Gallo said, referring to its molecular structure.

Nonetheless, scientists involved in the research learned to extract the anti-Kaposi's ingredient from urine. They call it HAF, for hCG-associated factor. For now, research is slowed by the laborious process of extracting tiny quantities from "hundreds of liters" of urine.

Once its molecular structure is found, Gallo said, the substance can be synthesized more easily.

Initially, Gallo viewed the substance only as a possible treatment for Kaposi's sarcoma. But his excitement grew during experiments with transgenic mice, animals that were altered to carry the gene for the human immunodeficiency virus in every cell. These mice don't get AIDS, but develop a syndrome that leads to death within two weeks of birth.

But baby mice given HAF through their mother's breast milk were protected. "You protect their life," Gallo said. "They live. When you stop the therapy, they get the disease."

A similar thing happened to laboratory monkeys who were infected with the simian immunodeficiency virus, a virus like the one that causes AIDS in humans. Treated monkeys maintained their normal weight, viral levels declined, and helpful immune cells rose.

"When we stopped the treatment, the monkeys died," he said.

Gallo said the compound probably does not fight the AIDS virus as effectively as protease inhibitors, the new generation of HIV-fighting drugs that have revolutionized treatment. "What is nice about it, however, is that it's without apparent toxicity," he said.

Scientists discovered that the substance promoted bone marrow when they administered it to marrow cells maintained in a laboratory dish.

Gallo's lab, which opened two years ago after state officials succeeded in wooing him to Maryland, has come under criticism in the Senate. A subcommittee two weeks ago said the institute should lose its state subsidy after next year. But House supporters disagreed, leaving the issue to be resolved by a conference panel.

Two leading AIDS researchers say they find the latest work exciting but advise caution. Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said the protein's greatest promise was as a bone-marrow promoter. "If it works, it has potential to work in a number of states where bone marrow is suppressed, as in chemotherapy."

Dr. David Schwartz, an AIDS researcher at the Johns Hopkins School of Medicine, said the work is intriguing because it points to a naturally occurring substance that is apparently safe.

"This is not a home run because it's not an identified compound yet, but I think it's quite an exciting observation," he said.

Pub Date: 3/31/98

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