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For the first time, researchers have shown that a cell-based therapy for HIV/AIDS can reduce the amount of virus in infected people. The breakthrough—big news for researchers, who have struggled for decades to create vaccines and cell-based therapies for HIV—was announced on Sunday at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago. To date, the sole treatment for HIV has been multidrug regimens that prolong life but never eliminate the virus.

Sangamo BioSciences of Richmond, California, says it has found a way to protect the T cells that HIV attacks first, so they can live to fight another day. The approach entails temporarily stopping a patient’s antiretroviral therapy and removing T cells carrying the CD4 receptor. This surface protein is the doorway by which the virus gains entry into the cell. The collected T cells are exposed to zinc finger nuclease, an enzyme designed to remove the gene for a coreceptor of CD4 called CCR5. The cells are then reinfused into the patient. Once they’re back in the body, the new study shows, the cells persist and travel in the body just like normal T cells.

Sangamo’s approach is based on the observation that some people have a naturally occurring mutation in the CCR5 gene that protects them against HIV. Ordinarily, humans have two copies of every gene. It turns out that individuals with a mutation in both copies of the CCR5 gene cannot be infected by the most common HIV strains. In people with the so-called Delta-32 mutation in just one copy of the gene, infection rarely progresses to AIDS. In the U.S., about 1 percent of the population is thought to carry the helpful mutation, which some researchers believe arose as protection against the Black Death.

Previous evidence existed showing that CCR5-negative cells could help AIDS patients. In 2007, an American man with AIDS and lymphoma received, as treatment for the cancer, a bone-marrow transplant from a person with the CCR5 mutation. The marrow recipient has been free of both AIDS and cancer since then. Sangamo’s method treats a patient’s own cells, with less risk than a marrow transplant.

“The data are very encouraging,” says Edward Lanphier, Sangamo’s founding CEO. “We are seeing a statistically significant correlation between our treatment and viral load reduction. This is a big step forward toward our goal of developing a functional cure for the disease.” Lanphier envisions that someday AIDS patients will not need to be on aggressive antiretroviral therapies because their virus will be well-controlled—or even undetectable, as happened with one subject with a mutation in one CCR5 gene.

Experts unaffiliated with Sangamo and its clinical trials agree that the scientific achievement is impressive, but they question the notion that it could yield a functional cure. Gerhard Bauer, assistant professor in the Stem Cell Program at the University of California, Davis, and director of that school’s Good Manufacturing Practice laboratory at the Institute for Regenerative Cures, says, “this is a great move forward, to demonstrate reduction of viral load by pushing in modified T cells. It has never been done before by any company, and I congratulate them 100 percent.”

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Tagged: Biomedicine, drugs, biology, HIV

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