San Francisco Chronicle - The Voice of the West, 901 Mission Street, San Francisco, CA 94119 - Wednesday, December 18, 1996 - Page A2
David Perlman, Chronicle Science Editor

The tests seek to supply AIDS patients with newly formed and fully functioning cells of their own immune systems that are genetically capable of preventing HIV, the AIDS virus, from reproducing after the virus has already infected them.

At a meeting last week of the American Society of Hematology in Orlando, Fla., scientists reported that they had successfully tested their new anti-HIV gene therapy concept in a remarkable colony of mice that were altered to carry the entire immune systems of humans rather than their own.

Now community-based physicians working with researchers at a Palo Alto company called SyStemix are about to recruit 60 volunteers -- some only recently infected with the AIDS virus, and others already ill with advanced HIV disease. The volunteers are to start receiving the experimental therapy early next month.

The team of physicians and molecular biologists intend to move slowly and cautiously during their first human trials because they know that what seems to work spectacularly in mice may well fail in humans, said Dr. Christopher Juttner, chief of medical research at SyStemix.

Some aspects of the effort to modify the immune system that does not involve gene therapy have already begun in attempts to halt the spread of various forms of cancer, and clinical trials of the work are under way in France and the United States in clinical trials of new approaches to prevent the spread of cancer, according to Juttner.

In the first gene therapy trial, which starts next month, doctors will remove bone marrow from the volunteers and separate out a crucial and highly specialized class of cells called stem cells that lie deep within the marrow of humans and animals.

Stem cells are known as the "mothers" of every person's complete blood supply. They are vitally important because within the marrow they continuously reproduce themselves and serve as the unique progenitors of all the body's red blood cells and platelets, as well as all the differentiated white cells that comprise each individual's immune system. Among that system's cells are the varied T-cells that are most often attacked by the invading AIDS virus and the macrophages that normally scavenge and devour the invaders.

After collecting each patient's purified stem cells, the researchers will then use tricks of molecular biology to insert into each stem cell copies of a single powerful gene known to AIDS scientists as the "rev gene." In its normal form, the rev gene makes a protein that regulates an essential early step that the virus must take to reproduce and spread.

In the trial, however, the scientists will use a harmless virus to insert a genetically altered form of the rev gene into the stem cells of the volunteer AIDS patients. That mutant gene, according to Juttner, should enable the reproducing stem cells to generate a full array of new immune system cells -- genetically capable of preventing the invading AIDS viruses from reproducing.

Hopefully, the transplanted mutant genes should provide each patient with a reconstituted and fully functioning immune system whose succeeding generations of stem cells, T-cells and macrophages will all be resistant to the AIDS virus.

The story of this new effort began at Stanford in the late 1980s when Dr. Irving Weissman, a pathologist and cancer biologist, first discovered how to isolate stem cells from bone marrow and purify them -- an achievement that scientists had been pursuing for 30 years.

Weissman and his research team then transplanted purified human stem cells from healthy humans into a specially bred strain of mice born with no immune systems of their own -- thus providing the mice with precisely the same immune systems that all healthy humans carry. Such mice, born with a hereditary condition called "severe combined immune deficiency," or SCID, are bred by the thousands in immunology research laboratories around the world.

Weissman continues to conduct his basic research at Stanford, but he is also on SyStemix's board of scientific advisers, and has played a key role in developing the wide range of anti-cancer efforts based on stem cell transplantation that the company is developing in partnership with Sandoz, the Swiss pharmaceutical firm.

The U.S. Food and Drug Administration approved the new gene therapy trials against AIDS two weeks ago. People with early HIV infections and late-stage disease are being enrolled this month, and the trials are expected to begin in early January and continue under careful monitoring throughout 1997 at AIDS clinical centers in Redwood City and Alabama.
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