Gene Therapy Hope for HIV: Engineered Stem Cells Hold Promise

Gene Therapy Hope for HIV: Engineered Stem Cells Hold Promise

 

 

When it comes to research on HIV and AIDS treatments, it can be hard to know when to celebrate a small advance–everyone wants to see progress, but so many experimental avenues that seemed promising have turned out to be dead ends. Still, a new study that tried a sophisticated form of gene therapy as an HIV treatment seems cause for cautious optimism. If it bears out under further testing, the technique could lead to a one-shot, long-lasting treatment that could replace the punishing regimen of daily medications.

Treating HIV currently comes down to controlling the viral load with a mixture antiretroviral drugs, but over time, this drug cocktail becomes less effective. Researcher John Rossi and his colleagues tried to craft a more permanent treatment by genetically modifying the HIV-infected patients’ own blood stem cells and increasing the cells’ ability to fight off the virus. The researchers weren’t able to truly combat the virus in this experiment–the patients’ viral loads remained the same–but their work moved beyond previous attempts in two ways: They successfully modified blood stem cells by giving them anti-HIV genes, and those cells survived for two years in patients.

Earlier clinical studies the group conducted with the same strategy made little headway, but now the researchers have overcome two key obstacles, says Rossi, a molecular geneticist. One is that they managed to stitch the anti-HIV genes into a high percentage of the appropriate stem cells. The other is that the cells lived for a long time. “If we could increase the number of modified cells by 10- or 100-fold, we might be able to stop the virus itself,” says Rossi. [ScienceNow]

The small study published in Science Translational Medicine tested the safety of the technique for HIV-infected patients, and served as a proof of concept. The four patients in this study were undergoing therapy for AIDS-related lymphoma at City of Hope cancer center in California. Part of the usual treatment for this condition is to remove blood stem cells (found in bone marrow) before cell-damaging chemotherapy, and to then return them after treatment. Researchers wanted to test their virus-fighting cells’ survival skills, so with each patient’s normal blood stem cells, the researchers also reintroduced a small number of modified cells.
They modified the cells in three ways: They boarded up the cells’ doors to keep the HIV virus out, and made two genetic changes to the cells’ internal defenses so that the virus would have a harder time copying itself if it made it through.

[T]he team added three genes to the immune stem cells’ DNA: one that cripples the CCR5 receptor that HIV exploits to enter the cell (this mimics a successful transplant recently done in Berlin with a much discussed patient who apparently was “cured” of his HIV infection), and two others that disable viral genes and prevent HIV from copying itself. This makes it increasingly difficult for HIV to find new targets and mops up any new virus produced [ScienceNOW].

As a safety precaution, the researchers didn’t implant enough of these novel cells to test how well they might fight the virus, but they did get a glimpse of how long the modified cells could stay in a person’s system. Up to two years after the treatment, patients still had low levels of these special cells.

“That’s a major finding,” Rossi added. While the number of cells expressing those genes was too low to provide any therapeutic benefit, it’s “proof of principle” that gene therapy may provide long-term HIV treatment, he said. [The Scientist]

As a next step, researchers hope to implant a greater number of modified cells in patients, to see how well they can fight and how long their defenses hold.