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Two chemicals boost immune cells' ability to fight HIV without gene therapy

A UCLA AIDS Institute study has discovered that two chemical compounds may help the immune systems of HIV-infected persons fight the disease without invasive gene therapy. Presented March 5 at the 2005 Palm Springs Symposium on HIV/AIDS, the new research demonstrates that the new chemicals activate telomerase -- a protein that boosts immune cells' ability to divide, enabling them to continue destroying HIV-infected cells.

"The immune cells that fight HIV naturally produce telomerase during the infection's early phase, but stop once HIV becomes a chronic condition," explained Rita Effros, Ph.D., Plott Endowed Chair in Gerontology and a professor of pathology at the David Geffen School of Medicine at UCLA. "The two compounds switched telomerase back on in the cells."

In earlier research, the UCLA team showed that inserting the telomerase gene into the immune cells of an HIV-infected person prevented the cells from aging prematurely. The telomerase enabled the immune cells to divide indefinitely, stimulated their production of a viral-fighting molecule and prolonged their power to kill HIV-infected cells.

In this study, the scientists isolated immune cells from the blood of HIV-infected persons and cultured the cells with the chemical compounds. They were surprised to see that the compounds produced the same three changes in the cells as those created by the gene therapy.

"Lo and behold, we discovered we didn't need to use gene therapy to reactivate the telomerase and strengthen the immune system's capacity to stave off HIV," said Effros, a member of the UCLA AIDS Institute. "We were thrilled to see we could create the same changes in the cells without relying on an invasive procedure."

Immune cells that battle HIV must constantly divide in order to continue performing their protective functions. The massive amount of division prematurely shortens these cells' ends, or telomeres, ultimately exhausting the immune system.

UC LA's previous research shows that telomerase rejuvenates the telomeres and allows the immune cells to remain youthful and active as they replicate under HIV's attack. Drugs that activate telomerase also offer therapeutic potential for a wide spectrum of degenerative diseases and chronic conditions in which cellular aging plays a role.

"I'm really excited by our findings. This progress moves us one step closer to drugs that work by switching telomerase on permanently and keeping the immune cells young and strong in their fight against infection," said Effros. "These therapies are also easier to develop than gene-therapy drugs."

The research was supported by a grant from the National Institute of Allergy and Infectious Diseases and a University of California Discovery Grant. Geron provided additional funding and the chemical compounds for use in the laboratory.

Effros' team included doctoral student Steven Fauce; Beth Jamieson, Ph.D., assistant professor hematology-oncology; and Otto Yang, Ph.D., associate professor of infectious diseases, all from UCLA.



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