Sepsis, the leading cause of hospital deaths, kills at least eight million people globally each year.
A bloodstream infection, in which the body's organs become inflamed and susceptible to failure, it can be caused by 6 species of fungi and 1400 species of bacteria. Diagnosis takes 2-5 days, and every hour you wait can increase the risk of death by 5-9%. The challenge grows with the rise in drug-resistant bacteria.
"Even with the best current treatments, sepsis patients are dying in intensive care units at least 30% of the time," says Mike Super, Senior Staff Scientist at the Wyss Institute for Biologically Inspired Engineering at Harvard University.
There is no therapy specifically approved to treat sepsis and the present standard of care is to provide patients with intravenous fluids and broad-spectrum antibiotics. Now a device from a team at Wyss may radically transform the way we treat sepsis.
"We are developing an entirely new approach ... that directly and quickly eliminates the pathogens and toxins that trigger the sepsis cascade," said Wyss Founding Director Don Ingber, M.D., Ph.D.,
The blood-cleansing device can be utilized quickly, even without identifying the infectious agent. In animal studies, treatment reduced the number of targeted pathogens and toxins circulating in the bloodstream by more than 99%.
Don Ingber and Mike Super tell the story of its development in the latest episode of Disruptive, the monthly podcast I produce with the Wyss Institute.
The seeds of the sepsis device go back over twenty years, in separate work undertaken by the two of them on separate continents. But it has been only four years since they began to collaborate on it at Wyss, and as Super points out, "That is incredibly fast."
Key to the technology is a genetically engineered protein based on a naturally occurring opsonin protein called Mannose Binding Lectin (MBL). In the human body, MBL binds to a wide range of pathogens in the blood stream and funnels them to be eliminated by the immune system.
The Wyss team fused the pathogen-binding portion of MBL to the Fc region of human immunoglobulin to yield the engineered FcMBL protein.
"The fusion protein had the capability of binding to many different pathogens that MBL has, but it also has the high level of expression, the ease of purification of the fc protein," Super points out.
Ingber adds, "This is where engineering comes in. Biologically inspired engineering is being inspired by the way nature builds. Then we want to take the best technologies we have from man-made approaches and engineering and science."
"So we took out the bad parts, kept in the good, put a bit of a molecule from an antibody at the bottom, because in the pharmaceutical industry they learned that that makes it incredibly easy to isolate it and purify it, so you can make large amounts of it cheaply. It also stabilizes it if you ever want to inject it in blood."
In a proof-of-principle study published in Nature Medicine, the team attached FcMBL to nanoscale magnetic beads and, in a device mimicking the spleen, demonstrated their ability to effectively clear a wide variety of pathogens and endotoxin from human blood samples.
In consultation with the FDA, they realized the need to simplify their technology. They eliminated the magnetic beads and instead of the microfluidic channels they'd been using, the improved device runs a patient's blood through a hollow, microfiber cylinder similar to filtering cylinders used with dialysis machines. The cylinders are coated with the FcMBL that captures both the pathogens causing the infection and the chemicals a patient's body creates to combat the infection. News of the redesigned device format was recently published in Biomaterials.
Explaining why he prizes people with industry experience like Mike Super, Ingber points out that, though the Wyss is embedded within an academic institution, "it really needed to be an institute that focuses from fundamentals to translation, and translation was the most novel thing that is not normally done in academia."
"We call it a technology translation engine. Measures of success in our original founding included IT portfolio patents; corporate alliances; licensing agreements; and new start-ups... Academics don't produce product, you have to develop a seamless interface with the industrial world." In keeping with that model, last week Wyss unveiled the launch of its startup company Opsonix Inc. to ready the sepsis therapy for clinical use.
Wyss release: http://wyss.harvard.edu/viewpressrelease/221