Inside-out cells offer target for antiviral drugs
November 23rd, 2008 : Category: Medical newsCHICAGO, Nov 23 (Reuters) - An experimental drug cured
guinea pigs infected with a fatal hemorrhagic fever virus,
raising hope for its use in a broad range of viral diseases
including influenza, hepatitis C, HIV, Ebola and others, U.S.
researchers said on Sunday.
"This is a whole new strategy for making antiviral drugs,"
said Dr. Philip Thorpe, professor of pharmacology at the
University of Texas Southwestern Medical Center at Dallas,
whose research appears in the journal Nature Medicine.
Instead of attacking the virus directly, bavituximab, made
by Peregrine Pharmaceuticals Inc (PPHM.O:
,
,
,
), takes advantage of a
defense mechanism used by the virus to hide from the immune
system, Thorpe said.
When cells are under attack by a virus, this stress causes a
fat molecule called phosphatidylserine, which normally lines the
inside of the cell, to flip to the outside. "It's like wearing
your clothes inside out," Thorpe, a scientific adviser to
Peregrine, said in a telephone interview.
Bavituximab, a genetically engineered antibody, seeks out
and attaches itself to these turncoat cells, flagging them for
the immune system, which can then mount an attack,
"When injected into the bloodstream, bavituximab circulates
in the body until it finds these inside-out lipids and then
binds to them," Thorpe said in a statement.
"In the case of virus infection, the binding raises a red
flag to the body's immune system, forcing the deployment of
defensive white blood cells to attack the infected cells."
Thorpe said conventional antiviral drugs try to exploit
some property of the virus, but these drugs are often quickly
defeated as the virus mutates.
By targeting an aspect of infected cells in the host, he
thinks bavituximab is less likely to lose effectiveness, which
commonly happens when a virus mutates.
In the study, Thorpe and his colleagues tested the compound
on guinea pigs in an advanced stage of infection with a form of
the Lassa fever virus, a disease that affects parts of West
Africa.
Half of the animals treated with the drug alone were cured.
When the researchers tested it in combination with the antiviral
drug ribavirin, a drug that keeps a virus from replicating, 63
percent of the guinea pigs lived.
Thorpe said the findings suggest the drug might be
effective on other types of hemorrhagic viruses, such as Ebola
and Marburg. But this lipid flipping also occurs in cells infected
with many other viral infections, including influenza, smallpox
and rabies.
Peregrine is conducting early phase clinical trials of the
drug in people with hepatitis C and human immunodeficiency virus,
or HIV, which causes AIDS. And it has more advanced trials under
way in cancer.
"We think it has tremendous potential," Steven King,
president and chief executive of Peregrine, said in a telephone
interview. Peregrine funded the research along with the
National Institutes of Health.
(Editing by Will Dunham and Todd Eastham)