'Hutch' gets $20 million grant to develop HIV cure
Seattle's Fred Hutchinson Cancer Research Center has been awarded a $20 million federal grant to study whether HIV could be cured by modifying an infected person's stem cells, part of a larger strategy by Hutch scientists to combat the virus that leads to AIDS.
Seattle Times staff reporter
Altering an HIV-infected person's stem cells not just to combat the virus that causes AIDS, but to eradicate it was — to many researchers — a pipe dream. Even the idea of a cure, while in the forefront of their minds, was thought improbable.
But a cure is exactly what Seattle's Fred Hutchinson Cancer Research Center will be pursuing with a $20 million, five-year research grant announced Monday by the National Institutes of Health.
"The field is now addressing the possibility of developing a cure, it was an abstract notion," said Hans-Peter Kiem, an expert in stem-cell transplantation and one of two principal investigators for this project. "To receive the resources to move this work forward is very exciting."
Two other research institutions received similar grants: the University of California, San Francisco, and the University of North Carolina, Chapel Hill.
The team of scientists at "The Hutch," in partnership with Sangamon Biosciences, a biopharmaceutical company based in Richmond, Calif., will be investigating a two-pronged approach aimed at eliminating HIV infection from the body.
Led by Kiem and his colleague, Keith Jerome, an expert in viral infections, the team will focus on ways of overcoming a major challenge to long-term control and a cure for the virus: existing HIV reservoirs, bits of genetic material that remains dormant in cells and tissue throughout the bodies of infected persons.
Those dormant pools of infection remain a threat during the person's life span. And while antiretroviral drug therapy has proved successful at helping patients keep HIV under control, it falls short of eliminating the reservoirs. If a person stops taking the drugs, the virus can rebound and begin infecting new cells.
The scientists plan to take an infected person's cells and make them HIV-resistant by eliminating a receptor on the surface of immune system cells that acts as a trap door for the virus to enter. This modification is meant to emulate a rare genetic mutation found in a remarkably small percentage of the population. Those modified cells are then reintroduced into the body, in a process similar to a bone-marrow transplant.
"We've been looking at HIV for many years and felt strongly that if we were ever going to cure it we had to go into the cells and modify them," said Kiem.
But Jerome and Kiem are careful not to raise false hope.
"Any results or treatment is still years away," said Jerome.
The 1990s saw the introduction of antiretroviral medication capable of keeping HIV in check by inhibiting the ability of the virus to replicate within the body.
In 1996, David Ho, director of New York's Aaron Diamond AIDS Research Center, announced that with 18 to 36 months of treatment, the virus could be eliminated. His claim proved false, as no combination of drug therapy could eradicate the viral reservoirs lurking in different regions of the body.
The Hutch group is modeling its work after a transplant approach that has been used successfully to treat cancers such as leukemia, but is relatively new in treating viruses. There is, however, one intriguing case that bodes well for their research: that of Timothy Ray Brown.
Known among research circles as the "Berlin patient," Brown was an HIV-positive man who in 2006 was diagnosed with leukemia, which, despite chemotherapy, persisted. His last chance was a stem-cell transplant from a bone-marrow donor.
His doctor hypothesized that a bone-marrow transplant from a person with the mutation for HIV-resistance would cure him not only of his leukemia, but his HIV, too. The transplant proved successful, as the HIV-resistant cells took over the man's immune system. Each new immune cell produced thereafter in the bone was resistant to the virus. Four years later, after countless blood tests and biopsies, Brown appears free of leukemia and HIV infection.
But experts, including Kiem and Jerome, agree that what cured Brown is not applicable to everyone. A stem-cell transplant is expensive and only a last resort. For this case to be relevant on a larger scale, Kiem and Jerome would have to successfully replicate the mutation, known as the delta 32 mutation, without a donor.
The second prong of the Hutch team's approach is to attack the virus head-on, by developing proteins to attack the viral reservoirs that sleep in places like the liver or brain, without harming the infected cells themselves. This attack plan is meant to complement the stem-cell transplants that would have already made the remaining cells immune to re-infection.
The end-goal to the project is to better understand how to modify stem cells and to successfully attack the virus, streamlining the process along the way.
"We really have many of the pieces of the puzzle here," said Kiem. "We have the ability to modify stem cells and transplants, ways of fighting the virus and hopefully a way to provide something meaningful to patients."
If all goes according to plan, human clinical trials are expected to begin in five years.
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