August 20, 2015

Harvard’s Wyss Institute improves its sepsis therapeutic device

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.

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