Christian Con Yost, M.D., associate professor of pediatrics at the University of Utah. He is corresponding author on a study published in The Journal of Clinical Investigation, showing that when given to mice, the newly discovered factor countered signs of sepsis, such as fever, fluctuations in respiratory rate, and death. Yost explains the research and next steps.">

Oct 3, 2016 — A factor found in umbilical cord blood could become the basis for a new therapy to fight sepsis, a leading cause of death in hospitals, explains Christian Con Yost, M.D., associate professor of pediatrics at the University of Utah. He is corresponding author on a study published in The Journal of Clinical Investigation, showing that when given to mice, the newly discovered factor countered signs of sepsis, such as fever, fluctuations in respiratory rate, and death. Yost explains the research and next steps.

Interview

Interviewer: A factor from cord blood shows promise in treating sepsis. Up next on The Scope.

Announcer: Examining the latest research and telling you about the latest breakthroughs, the Science and Research Show is on The Scope.

Interviewer: I'm talking with Dr. Christian Con Yost, assistant professor of pediatrics at the University of Utah. Dr. Yost, you have some study results that are receiving quite a bit of attention. What's this all about?

Dr. Yost: A lot of this really gets to ways to treat overwhelming infection and actually prevent some of the inflammatory tissue damage that can happen in syndromes like sepsis or other inflammatory disorders. I'm a neonatologist and I'm always interested in what can affect babies and cause them severe developmental problems or even death sometimes, but these are actually principles that could be applicable to many other disease states that happen in older children and even in some healthy or older adults.

Interviewer: I've actually seen quite a bit about sepsis lately. What is that exactly?

Dr. Yost: Sepsis is kind of the body's response to an infection that hasn't been completely controlled and actually that body's immune systems can actually be part of the process of damage. The body's response to an infection that isn't well controlled can lead to low blood pressure, can lead to [inaudible 00:01:26], all of the things that you'd associate with an overwhelming infection. If it's left unchecked and untreated, it can end up creating cardiac failure and lung failure that can lead to death.

Interviewer: So you've found a way or a factor that may help control sepsis and we'll get into the specifics of that in a bit, but there's something a little bit unusual about this factor. What is that? Where did it come from?

Dr. Yost: Yeah, that's an excellent question. In 2009, we published a paper that documented a novel immune deficiency in newborn babies. At that time there was a newly described part of the immune system called neutrophil extracellular trap formation. Our publication in 2009 documented for the first time that the neutrophils isolated from cord blood of newborn babies are not able to make these spiderweb-like nets that trap and kill bacteria. That was a novel finding in 2009.

Your question about where these inhibitory peptides come from that we'll be talking about, they really come from that finding and our interest in figuring out, okay, why can't these neutrophils from prematurely born babies or healthy term babies, when we isolate them from the umbilical cord blood, why can't they make nets? We were fortunate enough doing studies in babies here at the University of Utah and at Intermountain Medical Center to isolate a factor that really explains that.

Interviewer: What do these inhibitory peptides do then? They prevent that net formation altogether?

Dr. Yost: Yeah. These net inhibitory peptides circulate in the fetal circulation before birth and they are taken up by the neutrophils, these infection-fighting cells that are circulating both in the fetus and afterbirth and they stop net formation before it begins.

Interviewer: How did you go about showing that these peptides could have an effect on sepsis?

Dr. Yost: We actually developed or modified from the literature three different models of infection using the mouse as the model system. Using these models, we were able to show - and this might sound counterintuitive to many - that by inhibiting this specific part of the immune response, inhibiting net formation, that we actually increased survival in these mice treated with these peptides by about 40-60%. We're really excited about the results because while so much more research needs to be done, and it's very clear, we're very aware that some of the things that work in mice don't work in the actual patients, still these are grounds to really get excited about and our next steps will be testing this, not in humans yet but in more rigorous models.

Interviewer: Yeah. How are you thinking about how inhibiting this one very specific component of the inflammation response can have such a large impact?

Dr. Yost: As I kind of think about it in terms of overwhelming sepsis, it's not actually the bacteria that are creating so many problems for the patient. It's actually the body's response to that infection and the lengths that the body will go to try and attack it, it comes with collateral damage and sometimes that damage is very severe and can affect the vital organs - heart, lung, brain. When that happens, when you have this sepsis-like picture going on, if you can cool off a part of the inflammatory response net formation that is resulting in that inflammatory tissue damage, maybe at the expense of not killing as many bacteria, then the patient has more time for their body to recover, clear the infection, and for the physicians to manage the ventilator, manage the medications that support heart and lung function and allow that patient to, with the use of antibiotics to get better.

We would kind of look at these net inhibitory peptides, if I had to peek into that crystal ball and say how do I think these might be used in the future, we might look at these net inhibitory peptides as an adjuvant treatment when you make the diagnosis of severe sepsis and you start the appropriate antibiotics to cover what you think the bacteria or fungus or virus is. At the same time, you might be adding a net inhibitory peptide to cool off that part of the inflammatory cascade that researchers, us included, are showing can create a lot of inflammatory tissue damage and actually create the problems of sepsis that we're trying to treat.

I would not hesitate to suggest we might look at other autoimmune diseases such as lupus, such as rheumatoid arthritis. If net formation is part of the pathogenesis and the list of diseases that have disregulated net formation as part of that, I think our net inhibitory peptides could be looked at in that setting.

Announcer: Interesting, informative, and all in the name of better health. This is The Scope Health Sciences Radio.



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