Although the study involved only five people and years of extra work are needed, researchers said the results were a surprise and offer new hope in the field of gene therapy and for treating the fatal and incurable Aids virus.
“The goal of this phase one trial was safety and feasibility and the results established that,” said Dr Carl June of the University of Pennsylvania School of Medicine, who led the study.
“But the results also hint at something much more – it seemed to have a vaccine-like effect in that the immune system was better in most of the patients than when they enrolled. We are trying to study the mechanism.”
The Aids virus infects close to 40 million people worldwide and has killed 25 million. A cocktail of drugs can help control infection, but there is no cure and no vaccine.
The drugs also sometimes cause severe side effects in some patients and the virus can develop resistance so they have to move to new drug combinations.
Gene therapy is a promising but troubled field of research based on the premise that altering genes can cure disease.
It has cured only a few patients, and some have developed leukemia as a consequence. One gene therapy volunteer died in 1999.
June’s team tried a new gene therapy approach, first crippling the HIV virus, they report in this week’s issue of the Proceedings of the National Academy of Sciences.
“The virus is gutted so that it only has half the size of the original or pathogenic virus,” June said.
The so-called envelope gene remains, and is reversed, a manipulation called antisense.
The researchers then recruited five patients with HIV who were beginning to fail treatment, meaning the drugs no longer worked and the virus was beginning to damage their immune systems.
The world is struggling to check
June’s team removed the immune cells, CD4 T-cells, that are attacked by HIV.
The researchers infected the CD4 cells in the lab with their newly- engineered antisense HIV virus, then infused them back onto the patients.
When HIV or any other virus infects a cell, it injects its own genetic material into the cell. The cell is turned into a virus factory, sometimes pumping out thousands of copies of a virus before it explodes.
After the new antisense virus was infused, newly-infected cells pumped out defective virus, June said.
“The virus particles that are released are sterile. They are nonpathogenic,” June said.
This test was meant only to show that the approach was safe, and three years later, none of the patients show any ill effects.
The treatment appears to have helped restore the immune systems of four of the five patients, and the virus remains partly suppressed.
“We put back more [CD4 cells] than we took out. We don’t know if that is why their immune system gets better, because there are more soldiers, or whether it got better because of better antiviral effects,” June said.
The therapy is being developed by Gaithersburg, Maryland-based VIRxSYS and the studies are partly paid for by the National Institute of Allergy and Infectious Diseases.
Phase II trials are underway in HIV patients who have the disease well controlled by drugs.
June said it is not yet clear if the treatment could work only in infected patients, or might even be used as a preventive vaccine some day.