http://www.newscientist.com/article/mg20527454.200-drug-could-turn-soldiers-into-supersurvivors.html



*Drug could turn soldiers into super-survivors *

§  27 January 2010 by *Linda
Geddes*<http://www.newscientist.com/search?rbauthors=Linda+Geddes>

§  Magazine issue 2745 <http://www.newscientist.com/issue/2745>.
*Subscribe*<http://www.newscientist.com/subscribe?promcode=nsarttop>and
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§  For similar stories, visit the *Weapons
Technology*<http://www.newscientist.com/topic/weapons>and
*Death* <http://www.newscientist.com/topic/death> Topic Guides

A LUCKY few seem to be able to laugh in the face of death, surviving massive
blood loss and injuries that would kill others. Now a drug has been found
that might turn virtually any injured person into a "super-survivor", by
preventing certain biological mechanisms from shutting down.

The drug has so far only been tested in animals. If it has a similar effect
in humans, it could vastly improve survival from horrific injuries,
particularly in soldiers, by allowing them to live long enough to make it to
a hospital.

Loss of blood is the main problem with many battlefield injuries, and a
blood transfusion the best treatment, although replacing lost fluid with
saline can help. But both are difficult to transport in sufficient
quantities. "You can't carry a blood bank into the battlefield," says Hasan
Alam of Massachusetts General Hospital in Boston. "What we're looking for is
a pill or a shot that would keep a person alive for long enough to get to
them to a hospital."

We're looking for a pill that would keep a person alive for long enough to
get them to hospital

When the body loses a lot of blood, it tries to compensate by going into
shock. This is a set of emergency measures to raise blood pressure and
conserve energy, such as increasing heart rate and shutting down expression
of some proteins. However, if the body stays in shock for more than a short
time, it can lead to organ failure, and death soon follows.

Recent studies have suggested that around 6 or 7 per cent of genes change
their expression in response to shock, via the removal of "epigenetic",
chemical 
additions<http://www.newscientist.com/article/mg17924070.200-theres-more-to-inheritance-than-genes.html>to
the genome called acetylations. As histone deacetylase (HDAC)
inhibitors
can prevent the removal of such acetylations, Alam wondered if these drugs
might improve survival after blood loss.

His team previously showed that valproic
acid<http://www.newscientist.com/article/mg18725135.700-cheap-drug-could-polish-off-hiv.html>,
an HDAC inhibitor already used to treat epilepsy, increased survival rates
in rats that had lost a lot of blood. It seemed to be doing this by
preventing acetylation, causing certain "survival pathways" to remain
switched on.

Now Alam has repeated the study in pigs. He anaesthetised the animals,
drained 60 per cent of their blood, and subjected them to other injuries
before giving them a saline transfusion. He then injected some of the pigs
with valproic acid, gave others a blood transfusion and left the remainder
untreated.

Just 25 per cent of the pigs receiving only saline survived for 4 hours -
the typical time it takes to get hospital treatment - while 86 per cent of
those injected with valproic acid survived. All those that had a blood
transfusion lived (*Surgery*, DOI:
10.1016/j.surg.2009.04.007<http://dx.doi.org/10.1016/j.surg.2009.04.007>
).

Alam is currently repeating the trial to make sure valproic acid does not
hinder survival in the longer term. If so, he will apply for permission to
do human trials by the end of the year.

"It's exciting," says John
Holcomb<http://utsurg.uth.tmc.edu/faculty/holcomb-cv.html>of the
Center for Translational Injury Research at the University of Texas
in Houston. "They're looking at resuscitation in a different way."

Earlier studies by Alam's team showed that rats that naturally survive
traumatic blood loss also experience fewer changes in gene expression than
those that die or suffer complications. He thinks the same might be true in
humans. "Every person has this capacity to survive a huge insult, but most
of the time it's dormant," he says. "That's why the same insult kills some
people while others laugh and move on. What we're trying to do is make you
super-resistant using the pathways and proteins that already exist."

However, Graham
Packham<http://www.som.soton.ac.uk/about/staff/listing/profile.asp?gpackham>of
Southampton General Hospital, UK, who is investigating the use of HDAC
inhibitors to treat cancer, says it isn't yet clear how valproic acid, which
reacts with a wide range of molecules, is actually prolonging survival.
"It's not clear whether this is driven by valproic acid's epigenetic
activity," he says.

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