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The Q&A: Charles Cox

In this week's Q&A, we interview Charles Cox, a pediatric neurosurgeon at UTHealth and co-director of the Red Duke Memorial Hermann Trauma Institute.

Dr. Charles Cox, pediatric neurosurgeon at McGovern Medical School at UTHealth and co-director of the Red Duke Memorial He...

With each issue, Trib+Health brings you an interview with experts on issues related to health care. Here is this week's subject:

Dr. Charles Cox is a pediatric neurosurgeon at the McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth). He is also the co-director of the Red Duke Memorial Hermann Trauma Institute. He and his research team were recently awarded $6.8 million by the Department of Defense to test the safety and efficacy of stem cell therapy in adults with traumatic brain injury. We recently spoke with him to learn more about this research program.

Editor's note: This interview has been edited for length and clarity.

Trib+Health: Could you explain your research, and how it’s led to this Department of Defense award?

Charles Cox: I direct the pediatric trauma program at UTHealth and Children's Memorial Hermann Hospital in Houston. In pediatric trauma, traumatic brain injury (TBI) is realistically the primary unsolved problem in trauma.

We set out to really start to look at this area back in 2001. We had started working on this concept that certain stem cell-based therapies could repopulate the damaged tissue and kind of bridge the gaps between good cells and injured cells. At the time, that was the thinking. And there were some erroneous conclusions, based on preclinical data that was out there, that drove that.

Our first real significant observation was that, when you infuse these adult stem cells, they really aren't engrafting in the brain, and they really aren't transdifferentiating — that's the idea that they would turn into desired cells based on environmental cues of the tissue they were in — but we were seeing these functional benefits.

As time went on, more and more experiments and studies and papers, we then made the observation that these cells really are altering the body's innate immune response to injury.

Trib+Health: Could you explain how this immune response works, and how your research can help?

Cox: With TBI, your head hits the pavement, there’s a kinetic tissue disruption injury, and then after that is what's called a secondary brain injury. And that’s the body’s response to that damaged tissue. This has effects that cause cells and regions of the brain that are injured, but not all the way dead, to progress onto death. And you can have a low grade chronic neuroinflammatory response, that goes on for months, even years.

This progressive neuroinflammatory response is associated with progressive white matter loss. White matter, myelinated fibers, are really the connectivity of your brain. The connectivity is really what gives you higher order functioning. It’s what allows complex associated tasks, the executive functioning to occur. So the idea is, if we can mitigate that tissue loss over time, that will translate into improved outcomes.

That early secondary brain injury, that secondary neuroinflammatory response, is really what we are targeting with cell-based therapies. The idea is to kind of dampen but not turn off the body's inflammatory response.

The exciting part of this is there aren’t really any reparative therapies available for severe TBI. Everything you do right now is really supportive type treatment. And so that, to be able to impact that is exciting.

Trib+Health: What current therapies exist for TBI?

Cox: If there’s ongoing bleeding, we have surgery to stop that or evacuate the blood around the brain causing pressure on the brain. If that pressure has gotten so high, we either put a catheter into the space within the brain, where the spinal fluid is, and drain to reduce some of the pressure, or even remove a part of the skull and leave it off to relieve the pressure.

The problem with swelling is that it’s in a closed, hard case — your skull. There’s a very finite amount of expansion that can occur within your skull, before it’s so tight that it cuts off the blood supply.  

If there’s just swelling, and not bleeding driving it, then we use hyperosmolar therapies. Functionally, that's salt and sugar. We make it a little more fancy than that, but it’s a hypertonic saline solution that dehydrates the cells and sucks the water out of the brain, such that that swelling shrinks down. And then we can use some other medications, in terms of sedation, that help prevent the swelling as well. But that’s it.

It’s not like in cardiovascular diseases, where you have a specific abnormal rhythm in your heart, for example. They're going to give you a drug that binds in a very defined and specific way, to a very specific sub-receptor on the myocardium, and it’s going to change the way the electrophysiology in your heart functions. And they can titrate that with a lot of precision.

We don’t have that kind of tune-able small molecule medication that can really really effectively do that kind of thing.

Trib+Health: What does this award mean for your study? What will it allow you to accomplish?

Cox: It's a huge impact for us and our program. This is a phase II trial. What that means is phase I is safety, phase II is where you look for some type of a treatment effect, and then phase III is where that is broadened to multiple centers to see if it can be generalized out to a broader population.

Funding will take us through phase II. We plan to enroll 55 patients in this trial. So that would give us enough information to where we should be able to discern a treatment effect

Trib+Health: How significant is this health problem?

Cox: It's really incredible. Vast majority of TBI is mild — mild TBI happens all the time — sports injuries and that kind of thing. You slip and fall and hit your head. So mild TBI is the overwhelming majority of patients.

Severe TBI is the minority, but it makes up all the death. To give you some kind of big picture numbers: About 1.5 million people go to the ER in the U.S. with a TBI. About 300,000 each year are then admitted to the hospital, and about 50,000 a year die.

So you’ve got somewhere between 50 and 300 thousand patients a year that have between moderate and severe TBI. That ends up being billions of dollars per year in terms of economic burden.

The other kind of big picture thing to understand is — most people die from heart disease and cancer. But all those people are old folks. You take a healthy baby home from the hospital, the most common reason that they are going to die between age 1 and 44 is trauma.

It’s important how we understand and look at it — the significance of the problem is in young, quality adjusted life years that are lost. Not just death. And I think that's an important distinction

It's young people who are dying and are disabled from trauma. That's why it's important.

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