April 01, 2010

Stem Cell RNA Interference Treatment for HIV is Closer

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A novel stem cell therapy that arms the immune system with an intrinsic defence against HIV could be a powerful strategy to tackle the disease.

In the absence of an effective vaccine, daily administration of anti-retroviral drugs is the most effective treatment for HIV. However, low patient compliance rates combined with the virus's ability to easily mutate has led to the emergence of drug-resistant strains that are difficult to treat.



Professor Berkhout from the University of Amsterdam is investigating a novel gene therapy that has long-lasting effects even after a single treatment. It involves delivering antiviral DNA to the patients' own immune cells that arms them against viral infection. "This therapy would offer an alternative for HIV-infected patients that can no longer be treated with regular antivirals," he suggested.

The therapy involves extracting and purifying blood stem cells from the patient's bone marrow. Antiviral DNA is transferred to the cells in the laboratory, after which the cells are re-injected into the body. The DNA encodes tiny molecules called small RNAs that are the mirror image of key viral genes used by HIV to cause disease. The small RNAs float around inside the immune cell until they encounter viral genes which they can stick to like Velcro™. This mechanism, called 'RNA interference' can block the production of key viral components from these genes.

Transferring the antiviral DNA to stem cells would help to restore a large part of the patient's immune system. "Stem cells are the continually dividing 'master copy' cells from which all other immune cells are derived. By engineering the stem cells, the antiviral DNA is inherited by all the immune cells that are born from it," explained Professor Berkhout.

The group hopes to start clinical trials of the therapy within 3 years. "So far, very promising results have been obtained in the laboratory, and we are now testing the safety and efficacy in a pre-clinical mouse model," said Professor Berkhout.

Handheld HIV detector for $250 and other Cheap HIV tests

Researchers at California company Palo Alto Research Center have shrunk the laser technology inside large laboratory machines down to about the size of an iPod. Their cheap, handheld device promises to provide an immune system check-up on the spot and in less than 10 minutes.

The technology analyzes a small sample of blood drawn by a finger prick. Blood cells flow through a tiny channel, illuminated by a laser beam. A detector watches patterns in the light that bounces off the cells to identify them.

The detector looks for and counts CD4+ T cells, cells in the immune system that are killed by the HIV virus. The World Health Organization recommends that antiretroviral treatment begin when a patient's CD4 count drops below 250.

"The quality of their test is great," said researcher Bernhard Weigl of PATH, a non-profit reviewing a variety of CD4 testing technologies. "If you look at their graph, it pretty much looked like the graph you would get from a big instrument."

PARC's prototype cost about $250 to build, a hundred times cheaper than the large flow cytometers currently in use. Still, getting it to market may prove challenging.

Kiesel is competing against a dozen other groups vying to fill the need for cheap, portable CD4 tests. Other technologies have been under development for years, including a half-dozen recent projects funded by the Bill and Melinda Gates Foundation that include disposable CD4 tester kits as easy to use as a home pregnancy test. Kiesler's laboratory-tested device is a couple of years behind these projects, some of which have been tested in the field in African countries.

None of these devices is currently on the market. Many have been redesigned several times in the quest for commercialization, including a device by the Austin-based biotech company LabNow, which had hoped to have its technology on the market by 2006.

In the end, Weigl suspects that health workers will use some combination of these approaches in the field. Detectors like the one at PARC, with a low cost per person tested, make sense for areas with many cases of HIV, said Weigl. But disposable kits, which cost less initially and require no maintenance, may be a good solution for remote areas with fewer cases.

"I would be surprised if the first technologies aren't out by 2012," said Weigl. "The market is big; you're looking at many millions of users that have to get checked up every few months



A 20-year-old HIV-positive person starting antiretroviral (ARV) therapy today could expect to live, on average, to the age of 69, according to new calculations published July 26, 2008 in The Lancet. The study authors say this is a life expectancy increase of 37 percent over projections for 20-year-olds starting ARVs during the early years of combination treatment.


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