Treatment News : Novel Anti-HIV Gene Therapy Demonstrates Glimmers of Success

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June 17, 2010

Novel Anti-HIV Gene Therapy Demonstrates Glimmers of Success

The molecular pieces of an anti-HIV gene therapy—when given to HIV-positive people with lymphoma—persist in the blood for up to two years post-infusion, according to a study announced by researchers at City of Hope hospital in Duarte, California, and published June 16 in Science Translational Medicine. Though the experiment doesn’t prove that the new gene therapy can cure HIV, it does demonstrate that it’s safe and that the body doesn’t reject the treatment.

Much excitement and continued interest surround a stem cell transplant conducted two years ago in Germany that appears to have cured the recipient of his HIV infection. Gero Huetter, MD—the researcher responsible for the single-patient study—transplanted stem cells that carried a natural resistance to HIV infection in an HIV-positive man with leukemia. The new stem cells lacked the ability to produce a cellular coreceptor, called CCR5, which the virus uses when entering a cell. The transplanted cells were able to flourish, and two years later the man has no traces of HIV that can be found—in essence, he was cured of HIV.

Aside from the serious health risks of a stem cell transplant like the one Huetter performed, the procedure isn’t practical for most people, because it is rare to find a stem cell donor who both matches a person genetically—to reduce the risk that the body will reject the cells—and carries the CCR5 mutation. Thus, researchers around the globe are looking for other ways to accomplish the same goal.

In that vein, David DiGiusto, PhD, and his colleagues from City of Hope, designed an anti-HIV gene therapy for testing in four HIV-positive people scheduled to undergo a hematopoietic stem cell transplant for lymphoma. In this type of a procedure, a person’s own stem cells are extracted, combined with anti-HIV genes, expanded and then returned to the body.

Three anti-HIV genes were used by DiGiusto’s group: one that keeps the new cell from producing CCR5 receptors, one that has direct anti-HIV properties, and one that keeps the virus’s TAT protein from aiding the virus in reproducing once a cell is infected.

The cells treated with gene therapy were successfully and safely engrafted, and they appeared to persist at very low levels for up to 24 months following the transfusion.

DiGiusto’s team will now work on improving the process so that future recipients of the gene therapy can be given more of the cells during transplants than in the previous experiment—thus, hopefully allowing more of the cells to persist over time and boosting people’s resistance to HIV.

Search: Gene therapy, RNA interference, TAT, CCR5, lymphoma, Gero Huetter, cure, David DiGiusto, City of Hope

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