Health Check
Treating sepsis by protecting blood vessels shows promise
by Catharine Paddock
No specific treatment is currently available for sepsis - also
referred to as blood poisoning or septicemia - a life-threatening
condition that affects 19 million people worldwide every year. Now, a
new study shows that protecting blood vessels from the damage caused by
sepsis could be a way to successfully treat a condition that poses a
major challenge in the intensive care unit.
In the journal Science Translational Medicine, researchers from South
Korea describe how their approach - which targets the body's vascular
response as opposed to the infection itself or the body's inflammation
response - stopped mice from succumbing to sepsis.
The
treatment uses an unconventional antibody that converts a normally
harmful protein into a protective one.
Sepsis is a serious medical condition caused by an overwhelming
immune response to infection; it eventually damages the body's organs by
depriving them of nutrients and oxygen. In the worst cases, patients
spiral toward septic shock and multiple organs - lungs, kidneys, liver -
may quickly fail and cause death.
The condition - which is more common than heart attacks - is a
leading cause of hospital deaths. In the US, severe sepsis strikes more
than a million Americans every year, and estimates suggest between
28-50% of affected patients die - a higher number than deaths from
prostate cancer, breast cancer and AIDS combined.
Sepsis does not arise on its own but stems from other medical
conditions, such as an infection in the urinary tract, skin, lungs,
abdomen (such as appendicitis) or other part of the body. Invasive
medical procedures that accidentally introduce bacteria into the
bloodstream can also bring on sepsis.
'Strengthen the blood vessels'
One of the first things that happens in sepsis - when the immune
system overreacts and attacks the body - is that blood vessels become
weak and leaky. This results in a cascade of life-threatening effects,
ranging from severe inflammation and organ damage, to pulmonary edema
(fluid in the lungs) and death itself.
There is currently no cure for sepsis; doctors are only able to
target the underlying infection and hope that patients can find the
strength to fight the sepsis on their own.
The approach that the researchers behind the new study take is also
not exactly a cure for sepsis, but one that attempts to prevent and
protect the blood vessels from its worse effects and thus improve the
odds that the body can deal with the sepsis.
One of the study authors, Dr. Seung Jun Lee, a researcher at the
Institute for Basic Science in Daejeon, South Korea, says the purpose of
the treatment is to "strengthen the blood vessels so the body has a
stable environment to fight the infection which also prevents further
damage."
The method focuses on activating a receptor protein - called TIE2 -
that sits on the surface of cells in the lining of blood vessels. When
activated, TIE2 boosts the ability of the blood vessel lining to prevent
inflammation and leakage.
Antibody simultaneously blocks ANG2 and activates TIE2
Earlier attempts to boost the effect of TIE2, or reduce the effect of
ANG2 - a protein that blocks TIE2 - have either not been very effective
or are impractical for clinical use.
In the new study, the team used an antibody called ABTAA (short for
ANG2-binding and TIE2-activating antibody) that works by simultaneously
blocking ANG2 and activating TIE2. In their paper, the researchers
describe how it works:
"Upon binding to ANG2, ABTAA triggers clustering of ANG2, assembling
an ABTAA/ANG2 complex that can subsequently bind and activate TIE2."
Thus, by binding to it, ABTAA converts the normally harmful ANG2 into
a protein complex that boosts a protective effect.
In three different mouse models of sepsis, treatment with ABTAA
prolonged survival better than conventional ANG2 blockers.
The researchers also found that combining ABTAA antibody treatment
with antibiotics further enhanced survival from sepsis caused by
bacterial infection.
Experiments showed that the antibody stabilized blood vessels,
strengthened barrier function, and quelled systemic inflammation. This
offers the body a stronger battlefield to fight the infection, as Dr.
Lee explains:
"In the past, treating sepsis meant fighting off the underlying
infection but the immune system still attacked itself and people still
died."
The researchers suggest the new antibody could also be used as part
of a cure for other diseases that lead to leaky blood vessels, such as
Ebola, malaria and anthrax. They also suggest ABTAA may have a role in
reducing the severity of heart attacks, as they also cause major stress
on the body and increase production of ANG2.
Last year, Medical News Today learned of a study that found extreme
exercise may lead to sepsis.
- MNT
|