Researchers make AIDS breakthrough
Published: August 24, 2006
Discovery could have implications for cancer, other illnesses
A Montreal immunology team has announced a breakthrough discovery of a key component that’s baffled scientists in the fight against the AIDS epidemic: Why is the immune system not able to get rid of HIV-infected cells?
The answer, said Universite of Montreal lead investigator, Rafick-Pierre Sekaly, is that the body’s CD8 T-cells, the ”killer cells” of viral infections, become exhausted and quit functioning in HIV patients.
”We have discovered the mechanism that the virus is exploiting to undermine the immune system and makes it completely dysfunctional,” Sekaly said. ”Most important, we have shown that this can be reversed.
”We can correct his defect and this, for us, gives us great hope because a lot of other strategies have always failed.”
The finding means doctors might one day be able to manipulate a patient’s immune system into switching back on to fight HIV, cancer and infectious diseases.
Virologist Mark Wainberg, director of the McGill AIDS Centre at Montreal’s Jewish General Hospital, who was not involved in the study, called the breakthrough much broader than HIV.
”It’s not just relevant to HIV but to immunodeficiency in other disease states,” Wainberg said.
Sekaly’s team, which published its finding in the journal Nature Medicine, is heartened that two other teams led by Bruce Walker of Harvard Medical School and Richard Koup at National Institutes of Health, simultaneously reproduced similar results.
”All of us came to the same conclusion. It’s a rare occurrence for three teams,” said Sekaly, who worked with a group at the Royal Victoria Hospital led by McGill University Health Centre HIV/AIDS expert Jean-Pierre Routy.
”For us, it’s the first evidence that the HIV default can be reversed in the laboratory,” Routy said.
The Harvard, NIH and Montreal teams reported that blocking a molecule called PD1 (programmed death-1) restored the function of the T-cells.
While this worked against a chronic infection in mice, it’s more than just another complex animal model, Routy added. ”This blockade of an (overworking) gene leads to the clearance of the infection,” he said.
PD1 inhibits the function of the T-cells, Sekaly explained.
”We’ve shown that you can reverse the course of infection by waking up the immune system,” he said. ”A lot of other strategies have failed but now we can restore the function of CD8 cells and therefore the immune system.”
But tinkering with the immune system to switch it back on is risky because it could trigger autoimmune disease.
”The danger is that you could have a real overdrive,” Sekaly said, commenting on a botched London, England, trial of a drug to stimulate the immune system; in March, six healthy volunteer men landed in intensive care ‘’suffering from severe respiratory distress,” he said.
The Montreal team is involved in discussions to turn the research findings into treatment. Sekaly has sent HIV-infected blood samples to Medarex, a California drug company, for antibody testing.
Human safety and efficacy trials are to follow clinical trials in monkeys, which are planned during the next nine months, he added.
That’s the next step, said Anthony Fauci, director of the National Institute for Allergy and Infectious Diseases in the United States.
”We know they were able to do that in the test tube they were able to reverse the defect, which is an important advance,” he said, but it’s not yet known whether the same effect can be duplicated in the body.
”The bottom line isn’t in yet.”
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