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Scientists Tout Stem Cells' Use to Battle HIV
By Betsy Mason
CONTRA COSTA TIMES
Contra Costa Times (Walnut Creek, CA)
03 November 2005
SAN FRANCISCO
Nearly 10 years after the development of anti-viral drugs to treat HIV and AIDS, scientists are poised to attack the deadly virus with a new weapon: stem cells.
Researchers at UCLA are working on ways to arm blood stem cells in the bone marrow against HIV. Although the strategy does not amount to a cure, it may be more effective than current anti-viral treatments and some day might have the potential to immunize people against the virus.
HIV attacks several different types of blood cells that are part of the immune system. "If you can target the blood-forming stem cell, that cell gives rise to all blood cells," said virologist Jerome Zack of UCLA. "So, therefore, if you could protect that cell, then every other cell derived from that would be protected."
Zack presented his research Wednesday at a meeting of the Independent Citizens' Oversight Committee, the 27-member group created by Proposition 71 to direct the state's stem cell research program. The urgency to develop better treatments for HIV is particularly acute in San Francisco, where the disease has affected approximately 25 percent of the gay male population, said Robert Klein, chairman of the ICOC.
"Every day the situation gets worse," said Jeff Sheehy of the UC San Francisco AIDS Research Institute and an ICOC board member. "Every day 8,500 people in this world die of AIDS. Every day 14,000 new infections occur across the globe."
Current anti-viral therapies available to people with HIV and AIDS can suppress the virus and extend many patients' lives. But treatments involve a lifetime of daily medications with toxic side effects. Over time, resistance to the drugs can occur.
Zack said he hopes stem cell therapy could be a better strategy for fighting the virus. Along with UCLA's Ronald Mitsuyasu, a researcher and doctor who treats AIDS and HIV patients, Zack is devising a way to insert a gene into bone marrow stem cells that can either prevent HIV from infecting the cells or deactivate any virus already in the cells.
The idea is to replace the gene that is vulnerable to attack by HIV with a synthetically engineered piece of DNA designed to seek out and destroy the virus. The DNA fragment, known as a ribozyme, is tailored specifically to bind to HIV and cut it in half, rendering it harmless.
Mitsuyasu recently finished an initial clinical trial to test the safety of the treatment. The 10 patients in the trial did not have any problems, and after three years, the HIV-resistant blood cells could still be detected.
Mitsuyasu is currently enrolling people in a trial to test the stem cell therapy. Patients are first given a growth factor that stimulates bone marrow stem cells to enter the bloodstream. Then blood is drawn, and the patients' own stem cells are isolated from the blood. Next, the gene is inserted into the cells by a modified, harmless virus related to HIV. Then the stem cells, armed with their new weapon, are returned to the bloodstream, where they begin making all the different types of blood cells, each of which will inherit the new anti-HIV gene.
The method can protect about 10 percent of the patients' stem cells, but as HIV slowly kills the vulnerable cells and protected cells continue to replicate, the percentage will increase. To speed the process, six months after receiving the infusion of modified cells, patients will stop taking their anti-viral medications for four weeks to give the virus a chance to kill off some unprotected blood cells, putting pressure on the protected cells to replicate faster to replace them.
This is repeated again after 12 weeks, when the patients go off their medication for at least eight weeks and potentially longer, depending on how well the strategy works to reduce the level of HIV in the patients' blood. The trial will be finished in about a year and a half.
"If this works, even though it may not cure the disease, it certainly would allow patients to go for periods of time without therapy," Mitsuyasu said. "And that will make a big difference both in terms of the rate at which resistance develops to these medicines as well as all the side effects associated with having to take the medicine for the rest of their lives."
Reach Betsy Mason at bmason@cctimes.com or 925-847-2158.
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