Gene Therapy Shows Promise for Blocking HIV, Controlling AIDS

http://www.businessweek.com/news/2010-06-16/gene-therapy-shows-promise-for-blocking-hiv-controlling-aids.html

Two cutting-edge medical technologies, stem cell transplantation and gene therapy, were combined in an attack on the AIDS virus that may lead to new strategies for treating people infected with HIV.

Researchers at the City of Hope, a nonprofit research institute near Los Angeles, extracted stem cells from the blood of four people with AIDS-related lymphoma, a blood cancer, and modified some of them to carry anti-HIV genes. The altered cells were returned to the patients’ blood without harming them and remained there for two years, a sign that if given in greater number, they might be able to suppress the AIDS virus.

The results may help researchers hunting for ways to cure HIV patients or block the AIDS virus without putting people on toxic medicine for the rest of their lives. Potent antiviral drugs suppress the virus and allow those infected to live near- normal lives. Yet the medicines are unaffordable to millions in poor countries and cause side effects that may shorten the lives of people who use them.

“One of the problems with antiviral therapy is that it has almost led to the perception that HIV is cured and that’s not true,” said David Schaffer, a professor of bioengineering at the University of California, Berkeley, who co-directs the school’s stem cell center. “If you could develop a therapy to make HIV-proof blood cells, then you could create a true cure for HIV. This is a very promising clinical trial that takes us in that direction.”

Schaffer, who was not involved in the research, wrote a commentary accompanying the study. Both were published today in the journal Science Translational Medicine.

Current Treatments

More than 34 million people worldwide are infected with HIV, the virus that causes AIDS, and about 2 million lost their lives to AIDS in 2008, according to the World Health Organization, based in Geneva. Efforts to develop vaccines to prevent high- risk people from becoming infected have so far failed, leaving the drug cocktails made by companies led by Gilead Sciences Inc., based in Foster City, California, and London-based GlaxoSmithKline Plc as the method of treating people with HIV.

The City of Hope research builds on an experiment reported last year by a German doctor, Gero Hutter, in the only known case of an AIDS patient being cured. The patient, who had AIDS and leukemia, was given a stem-cell transplant from a donor whose rare gene variant caused his immune cells to lack a receptor called CCR5. Without this receptor, HIV can’t infect immune cells.

New Blood

Hutter’s patient had his blood-forming stem cells wiped out and replaced by those of the donor. The transplant rebuilt his blood system and cured his leukemia. His immune cells also became resistant to HIV, allowing him to stop the antiviral drugs he’d been taking for 10 years.

Three years after the transplant, the patient still has no detectable HIV, Hutter said in a June 5 interview. The City of Hope researchers extracted patients’ blood- forming stem cells, genetically modified some of them and infused them back into the patients after first wiping out their bone marrow and blood system.

The modified cells were altered using a harmless virus to carry three different gene sequences into them. This triple- therapy approach was modeled on drug cocktails that attack HIV in multiple ways to overcome drug resistance, study leader John Rossi said in a June 14 telephone interview.

One of the molecules cuts the CCR5 sequence in an effort to bar the door to a cell and keep HIV from entering, the second squires away a protein that the virus uses to replicate and the third knocks out a key piece of genetic machinery that HIV needs to maintain itself, Rossi said.

Multiple Attacks

“The idea is to hit multiple sites of the virus with different types of gene therapy so resistance to one doesn’t make it resist others,” Rossi said. “The three work better than any two together.”

The transplant procedure is risky and was only attempted on HIV patients who needed it to treat their cancer. All four patients remain free of their lymphoma about two years after the treatment, Rossi said.

The number of gene-modified cells returned to the patients in the study was too small to cure or even improve their HIV infections, Rossi said. The next step is to replace a much larger portion of a patient’s stem cells with gene-modified cells and see if they can substantially reduce their HIV level.

Rossi and his colleagues also are exploring ways to alter the transplant procedure to make it less toxic. That may allow the procedure to be used on HIV patients who don’t have cancer.

The research was funded in part by Benitec Ltd., a Melbourne, Australia-based biotechnology company that developed one of the gene therapy treatments used in the trial.

June, 16 2010 (Bloomberg)