From: KutchScience

Sent: Tuesday, November 07, 2006 7:16 PM
Subject: HIV gene therapy 'shows promise'
http://news.bbc.co.uk/1/hi/health/6120042.stm


Dear Docs, Medicos and friends of Science and Genetics,

HIV gene therapy 'shows promise' http://news.bbc.co.uk/1/hi/health/6120042.stm
Gene therapy is complex and would be a totally different strategy for HIV
treatment -Roger Pebody Terrence Higgins Trust
HIV attacks immune cells

Preliminary tests suggest HIV infection can be treated using a disabled version
of the virus itself.
University of Pennsylvania researchers treated five patients, who had not
responded to drugs, with disabled HIV. It carried added genetic material that
blocks HIV reproduction and as a result HIV levels in the patients' blood either
stabilised or decreased. The research raises the prospect that gene therapy
might provide an alternative to antiretroviral drugs. The long-term
effectiveness of the drugs is under threat from the growing problem of drug
resistance. Researcher Dr Carl June said: "Gene therapy has long been discussed
as an alternative treatment for HIV. "The goal of this trial was safety and
feasibility and the results established that. "But the results also hint at
something much more." The patients selected for the trial had failed to respond
to at least two antiretroviral regimens of drugs.

Own cells

They were given a single infusion of their own immune system T cells that had
been removed from their blood, purified and genetically modified to carry the
manipulated version of HIV. Each patient received around 10 billion T cells -
between 2% and 10% of the total number in an average person. The disabled HIV
gene used by the researchers was modified to carry an antisense RNA molecule,
which scrambles the process of reading genetic information and is designed to
sabotage the process HIV uses to reproduce itself inside infected cells. Viral
loads of the patients remained stable or decreased during the nine month trial -
and one subject showed a sustained dramatic decrease in viral load. T-cell
counts remained steady or increased in four of the five patients. The
researchers were able to detect the modified cells in patients for months, and
in some cases years after the infusion. However, they warn that the trial was
very small, and said patients would be monitored for 15 years to assess
long-term effects.

Dr Bruce Levine, who also worked on the study - published online in Proceedings
of the National Academy of Science - said: "Just because this has produced
encouraging results in one or two patients doesn't mean it will work for
everyone. We have much more work to do." Dr George Schmid, a specialist in HIV
at the World Health Organization, said it could take many years to determine
whether the technique was safe and effective, but he said the results were
"encouraging". Roger Pebody, of the charity Terrence Higgins Trust, said: "Gene
therapy is complex and would be a totally different strategy for HIV treatment.
"Although in its early stages, this research seems to indicate that this
approach may be safe and the results are hopeful." Edwin Bernard, editor of the
journal Aids Treatment Update, said gene therapy was likely to be a
labour-intensive, expensive treatment designed for individuals, and so not
available to the vast majority of people with HIV/Aids who live in developing
countries. He said new drug treatments currently under development might provide
an alternative.

Wider applications

It is hoped the approach could be adapted to tackle other diseases. The
researchers believe the use of viruses like HIV, lentiviruses, may prove
particularly effective in gene therapy. Lentiviruses are especially effective at
infecting T cells, and also infect non-dividing or slowly dividing cells,
raising the prospect that they could be used to target neurons or stem cells.
They also insert themselves into the DNA of cells in such a way that may make
them safer and able to produce more long-term effects than other potential gene
therapy vectors, such as adenoviruses. The researchers are now recruiting for a
second trial of the treatment - dubbed VRX496. This time it will be tested on
patients whose HIV load is already well controlled by existing drugs. The hope
is that these patients will be able to stay off their antiretroviral drugs,
which do have significant side effects, for an extended period.

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