Triple-punch gene therapy for AIDS patients

[Boze]

http://timesofindia.indiatimes.com/life/health-fitness/health/Triple-punch-gene-therapy-for-AIDS-patients/articleshow/6058274.cms

Triple-punch gene therapy for AIDS patients
ANI, Jun 17, 2010, 01.21pm IST
A triple-punch gene therapy, which endows human stem cells with three ways to resist HIV, has successfully cleared its first safety test in humans.

Four patients with AIDS who were infused with these cells tolerated the treatment, and the cells produced their anti-HIV weapons for up to two years.

While not many cells were transplanted in the trial to cure the patients or even reduce their viral load, researchers are hopeful that after further clinical trials, combination gene therapy may replace or complement anti-retroviral drugs as a way to treat people living with HIV.

The trial piggybacked on a standard treatment, in which individuals with AIDS receive transplants of their own previously saved blood stem cells, in an attempt to prevent the development of lymphoma (blood cancer).

In addition to normal blood stem cells, the patients were also given cells into which three types of RNA-based gene therapies were carried by a lentivirus.

In the current trial, the researchers engineered a combination of genetic resistance into stem cells, aiming to replace an immune system susceptible to HIV with one able to resist the virus’s attack.

Firstly, to stop HIV from penetrating the host cells, the researchers gave the cells an RNA enzyme that would cleave the message that codes for a protein called CCR5, preventing HIV from using the protein as a co-receptor to enter the cell.

"We know from a lot of populations that this is a great target — it can downregulate (HIV levels) by 90 per cent," Nature quoted John Rossi, a molecular biologist at the Beckman Research Institute of the City of Hope in Duarte, California, who worked on the trial, as saying.

But interfering with CCR5 is not foolproof, because HIV can evolve other ways of penetrating the cell.

"If somehow the virus should get into these cells, then we have the cells armed with two different approaches" to fight back, explained Rossi.

So the researchers used a second mode of attack, and inserted a decoy RNA that interferes with a viral protein called tat, which is important for replication.

Third, they used a technique called RNA interference (RNAi), in which they deployed a short sequence of RNA to degrade the message coding for that same viral protein and one of its partners in crime.

Such different mechanisms will make it harder for viral resistance to develop, noted Rossi.

In three of the four patients, the blood stem cells continued to produce these RNAs 18–24 months after they had received the transplant. The patients also showed no adverse reactions to the vector — a long-standing concern with gene therapy.

"It’s a small study, but it’s a step in the right direction. The most promising thing is that it shows you can modify stem cells in a way that makes them (HIV-)resistant, and the progeny of those cells would still be resistant to HIV and would still be functional," said Pablo Tebas, a clinical researcher at the University of Pennsylvania in Philadelphia who works on gene therapy and vaccines for HIV.

The study is published in Science Translational Medicine1 .

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Xman - I hope you like this news

[Boze]

same story but reported in a different news outlet, more detail.

http://www.businessweek.com/print/lifestyle/content/healthday/640197.html

Gene Therapy for HIV Inches Forward
Viable treatment is still a long way off, researchers say
By Randy Dotinga
HealthDay Reporter

WEDNESDAY, June 16 (HealthDay News) -- Researchers report they've moved a step closer to treating HIV patients with gene therapy that could potentially one day keep the AIDS-causing virus at bay.

The study, published in the June 16 issue of the journal Science Translational Medicine, only looked at one step of the gene therapy process, and there's no guarantee that genetically manipulating a patient's own cells will succeed or work better than existing drug therapies.

Still, "we demonstrated that we could make this happen," said study lead author David L. DiGiusto, a biologist and immunologist at City of Hope, a hospital and research center in Duarte, Calif. And the research took place in people, not in test tubes.

Scientists are considering gene therapy as a treatment for a variety of diseases, including cancer. One approach involves inserting engineered genes into the body to change its response to illness.

In the new study, researchers genetically manipulated blood cells to resist HIV and inserted them into four HIV-positive patients who had lymphoma, a blood cancer.

The patients' healthy blood cells had been stored earlier and were being transplanted to treat the lymphoma.

Ideally, the cells would multiply and fight off HIV infection. In that case, "the virus has nowhere to grow, no way to expand in the patient," DiGiusto said.

At this early point in the research process, however, the goal was to see if the implanted cells would survive. They did, remaining in the bloodstreams of the subjects for two years.

In the next phases of research, scientists will try to implant enough genetically engineered cells to actually boost the body's ability to fight off HIV, DiGiusto said.

Plenty of caveats still exist. The research, as DiGiusto said, is experimental. And there's the matter of cost: He estimated that the price for gene therapy treatment for HIV patients could run about as much as a bone marrow transplant. Those cost about $100,000.

On the other hand, gene therapy has the potential to free HIV patients from a lifetime of taking medications that may fail to work, especially if the virus develops immunity to them, said David V. Schaffer, co-director of the Berkeley Stem Cell Center at the University of California at Berkeley and co-author of a commentary accompanying DiGiusto's study.

Over time, the savings on medications could outweigh the cost of the gene therapy, he noted.

The treatment wouldn't necessarily be a cure because the virus would remain in the body. Still, it could create a situation "where HIV is present but at levels that are too low to detect and don't cause AIDS," Schaffer said.

[Hellraiser]

4 years of Atripla = $100,000.  More upfront but if it works then it would be more cost effective in the long run.

[Inchlingblue]

This is already being discussed in another thread:

http://forums.poz.com/index.php?topic=27363.msg408131#msg408131

[Boze]

4 years of Atripla = $100,000.  More upfront but if it works then it would be more cost effective in the long run.

It's about $1k a month I thought - so about 8 years. But I think that as with any technology, the more it's used, the cheaper it will get.

This is already being discussed in another thread:

http://forums.poz.com/index.php?topic=27363.msg408131#msg408131

Thanks - didn't see that one.

[Inchlingblue]

It's about $1k a month I thought 

$1K a month sounds low even in the UK where the NHS is able to negotiate prices with pharmaceuticals but in the US it's in the ball park of $2K a month (most triple drug combos are in that ball park in the US, give or take a couple hundred dollars).

Anyone with a chronic condition living in a country that provides its citizens with health care should consider themselves very fortunate indeed.

[Boze]

$1K a month sounds low even in the UK where the NHS is able to negotiate prices with pharmaceuticals but in the US it's in the ball park of $2K a month (most triple drug combos are in that ball park in the US, give or take a couple hundred dollars).

Anyone with a chronic condition living in a country that provides its citizens with health care should consider themselves very fortunate indeed.

Ahh, ok. Yes - 1k is the price that NHS pays (625 gbp).