This video
explains how sepsis induced by an overload of blood pathogens can be
treated with the
Wyss Institute’s improved pathogen-extracting, spleen-mimicking device.
Blood is flown
through a cartridge filled with hollow fibers that are coated with a
genetically
engineered blood
protein inspired by a naturally occurring human molecule called
Mannose Binding
Lectin (MBL). MBL is activating our innate immune system when
bound to toxic
invaders, marking them for capture by immune cells in the spleen.
Credit: Wyss
Institute at Harvard University
The Institute's blood-cleansing device, enabled by a
genetically engineered pathogen-capturing protein, has been simplified to
accelerate its clinical translation
(August 20, 2015) Last
year, a Wyss Institute team of scientists described the development of a new
device to treat sepsis that works by mimicking our spleen. It cleanses
pathogens and toxins from blood circulating through a dialysis-like circuit.
Now, the Wyss Institute team has developed an improved device that synergizes
with conventional antibiotic therapies and that has been streamlined to better
position it for near-term translation to the clinic. The improved design is
described in the October volume 67 of Biomaterials.
Sepsis is a common and frequently fatal medical complication
that can occur when a person's body attempts to fight off serious infection.
Resulting widespread inflammation can cause organs to shut down, blood pressure
to drop, and the heart to weaken. This can lead to septic shock, and more than
30 percent of septic patients in the United States eventually die. In most
cases, the pathogen responsible for triggering the septic condition is never
pinpointed, so clinicians blindly prescribe an antibiotic course in a blanket
attempt to stave off infectious bacteria and halt the body's dangerous
inflammatory response.
But sepsis can be caused by a wide-ranging variety of
pathogens that are not susceptible to antibiotics, including viruses, fungi and
parasites. What's more, even when antibiotics are effective at killing invading
bacteria, the dead pathogens fragment and release toxins into the patient's
bloodstream.
The
blood-cleansing device connected to a dialysis-like circuit is harboring
a dense pack of
parallel running hollow fibers whose inner surfaces are covered
with the Wyss
Institute’s genetically engineered Mannose-binding lectin (MBL) protein,
called FcMBL. When
septic blood is streamed through the device, FcMBL effectively
extracts viruses,
fungi and parasites as well as toxins and dead pathogen fragments
released into the
bloodstream by antibiotic killing. Credit: Wyss Institute at Harvard University
"The inflammatory cascade that leads to sepsis is
triggered by pathogens, and specifically by the toxins they release," said
Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who leads the Wyss
team developing the device and is the Judah Folkman Professor of Vascular
Biology at Boston Children's Hospital and Harvard Medical School and Professor
of Bioengineering at the Harvard John A. Paulson School of Engineering and
Applied Science. "Thus, the most effective strategy is to treat with the
best antibiotics you can muster, while also removing the toxins and remaining
pathogens from the patient's blood as quickly as possible."
The Wyss team's blood-cleansing approach can be administered
quickly, even without identifying the infectious agent. This is because it uses
the Wyss Institute's proprietary pathogen-capturing agent, FcMBL, that binds
all types of live and dead infectious microbes, including bacteria, fungi,
viruses, as well as toxins they release. FcMBL is a genetically engineered
blood protein inspired by a naturally-occurring human molecule called Mannose
Binding Lectin (MBL), which is found in the innate immune system and binds to
toxic invaders, marking them for capture by immune cells in the spleen.