$5.6 million CIRM grant will advance studies of new HIV treatment

June 12, 2014 | by

A $5.6 million CIRM grant will allow a new approach to treating HIV to enter clinical trials.

A $5.6 million CIRM grant will allow a new approach to treating HIV to enter clinical trials.

A new approach to treating HIV could free patients from the virus’ tyranny once and for all. That approach will now advance to clinical trials, led by City of Hope researchers, through a $5.6 million grant from the California Regenerative Medicine Institute.

Under the leadership of John A. Zaia, M.D., chair of the Department of Virology and the Aaron D. Miller and Edith Miller Chair in Gene Therapy, a team of investigators at City of Hope, Sangamo Biosciences and Keck School of Medicine of USC have been developing a combination stem cell and gene therapy approach. Sangamo will provide an equal amount of funding to advance the project.

In the collaboration, AIDS patients from USC will receive treatment at City of Hope and then return to USC for follow-up.

“This is an important start that could one day change the way HIV/AIDS is treated,” Zaia said.

Although drug therapies aimed at holding back HIV, the virus that causes AIDS, have advanced significantly, they do not prevent continued virus growth and they have significant side effects. A cure remains elusive.

Several years ago, a surprise development gave hope that a genetic modification of blood stem cells could provide that cure. An AIDS patient became free of HIV infection after he received a bone marrow transplant to treat his leukemia. Dubbed the “Berlin patient,” he received marrow from a healthy donor who had a rare mutation that prevents the production of a key protein that the virus needs to infect cells. Essentially, the donor marrow was immune to HIV infection.

The scarcity of this mutation among marrow donors prevents additional cures using transplantation; however, the approach that City of Hope researchers are exploring could get around that problem. Their method targets this same key protein that HIV needs to infect cells.

Using an enzyme called a zinc-finger nuclease (ZFN), the research team can create a mutation in the protein. They can “edit” the HIV patient’s stem cell genes so that, like the Berlin patient’s donor, they can no longer produce the protein. No protein, no HIV infection. The virus might then disappear from the body.

This study will be the first trial of ZFN technology in human stem cells. Earlier clinical studies in HIV-positive patients show that the ZFN method is generally safe when used with white blood cells called lymphocytes. And in one patient, the therapy was associated with temporary control of HIV without antiviral medication.

The current grant will extend the clinical studies to stem cells of HIV patients who have had poor responses to standard therapies. The aim is to determine if the modified stem cells are safe for these patients and if they remain present in the body and effective over time.

The scientists hope to begin treating these patients by autumn.


Learn more about research at City of Hope.


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