Health

AIDS gene therapy research is promising

Scientiests have used genetic engineering in six patients to develop blood cells that are resistant to HIV.

Genetic engineering used to develop resistant blood cells.

Jay Johnson took part in one of the studies testing gene therapy as a possible new way to treat and perhaps someday to cure infection with HIV. FEB. 25, 2011 (Matt Rourke/Associated Press)

In a bold new approach ultimately aimed at trying to cure AIDS, scientists have used genetic engineering in six patients to develop blood cells that are resistant to HIV, the virus that causes the disease.

It's far too early to know if this scientific first will prove to be a cure, or even a new treatment. The research was only meant to show that, so far, it seems feasible and safe.

The concept was based on the astonishing case of an AIDS patient who seems to be cured after getting blood cells from a donor with natural immunity to HIV nearly four years ago in Berlin.

Researchers are seeking a more practical way to achieve similar immunity using patients' own blood cells.

The result, announced Monday, at a conference in Boston left experts cautiously excited.

"For the first time, people are beginning to think about a cure" as a real possibility, said Dr. John Zaia, head of the government panel that oversees gene therapy experiments.

This is the first time researchers have permanently deleted a human gene and infused the altered cells back into patients. Other gene therapy attempts tried to add a gene or muffle the activity of one, and have not worked against HIV.

Even if the new approach doesn't get rid of HIV completely, it may repair patients' immune systems enough that they can control the virus and not need AIDS medicines — "what is called a functional cure," he said.

Carl Dieffenbach, AIDS chief at the U.S. National Institute of Allergy and Infectious Diseases, agreed. "We're hopeful that this is sufficient to give the level of immune reconstitution similar to what was seen with the patient from Germany," he said. 

This is the first time researchers have permanently deleted a human gene and infused the altered cells back into patients. Other gene therapy attempts tried to add a gene or muffle the activity of one, and have not worked against HIV.

The virus can damage the immune system for years before people develop symptoms and are said to have AIDS — acquired immune deficiency syndrome. The virus targets special immune system soldiers called T-cells. It usually enters these cells through a protein receptor, or "docking station," called CCR5.

Some people (about 1 percent of whites; fewer of minorities) lack both copies of the CCR5 gene and are naturally resistant to HIV. One such person donated blood stem cells in 2007 to an American man living in Berlin who had leukemia and HIV.

The cell transplant appears to have cured both problems, but finding such donors for everyone with HIV is impossible, and transplants are medically risky.

Warning that results could be overstated

So scientists wondered: Could a patient's own cells be used to knock out the CCR5 gene and create resistance to HIV?

A California biotechnology company, Sangamo BioSciences Inc., makes a treatment that can cut DNA at precise locations and permanently "edit out" a gene.

Dr. Jacob Lalezari, director of Quest Clinical Research of San Francisco, led the first test of this with the company and colleagues at the University of California in San Francisco and Los Angeles.

He warned that it would be "way overstated" to suggest that the results so far are a possible cure.

"It's an overreach of the data. There are a lot of people out there with hopes and dreams around the C-word," so caution is needed.

In the study, six men with HIV had their blood filtered to remove a small percentage of their T-cells. The gene-snipping compound was added in the lab, and about one-fourth of the cells were successfully modified. The cells were mixed with growth factors to make them multiply and then infused back into the patients.

"The cells are engrafting — they're staying in the bloodstream, they're expanding over time," said Lalezari, who has no personal financial ties to Sangamo, the study's sponsor.

The only side effect was two days of flu-like symptoms. It will take longer to determine safety, but several AIDS experts said they were encouraged so far.

On Wednesday, Dr. Carl June, a gene therapy expert at the University of Pennsylvania, will report partial results from a second, federally funded study of 10 people testing Sangamo's product. He treated his first patient with it in July 2009.

Jay Johnson, 50, who works for Action AIDS, an advocacy and service organization in Philadelphia, had the treatment in September.

"My results are excellent," he said. "The overall goal is to not have to take medication, and then hopefully lead maybe to a cure."

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