How a protein called 'NFL' could help the NFL with brain injuries

Capital Gazette

Brain injuries are a danger in many sports, but for none more than football and its most profitable enterprise, the National Football League. The NFL is spending hundreds of millions of dollars on a concussion-lawsuit settlement and has poured tens of millions into research on measuring and preventing head trauma.

Now some scientists are using an NFL-backed technology to examine blood samples for proteins that have been shown to correlate with concussion and other injuries. One of the most intriguing of these proteins, which could help create better tests for traumatic brain injury, is called neurofilament light — or, as it's known for short, NFL.

That's right, a protein called "NFL" may wind up helping the NFL address its most vexing medical problem.

"It's just a remarkable coincidence," said Kevin Hrusovsky, chief executive of Quanterix, a company that has received $800,000 in grant money from the NFL through the league's "Head Health Challenge" partnership with GE. Quanterix's technology allows users to zero in on molecules with such precision that Hrusovsky likened it to "being able to see a grain of sand in 2,000 Olympic-size swimming pools."

That is crucial, because only tiny amounts of the proteins, referred to as "biomarkers," dribble across the blood-brain barrier from the cerebrospinal fluid around the brain, where they would be found in larger quantities. The ability to spot sub-concussion injuries is important because they often go undetected by conventional methods and yet are increasingly seen as major threats to long-term health.

The problem with simply sampling athletes' cerebrospinal fluid, of course, is that requires a lumbar puncture, or spinal tap, which is a lot to ask in the middle of a football game (or in any other time and place, for that matter). Pricking an athlete's finger for a blood test and getting the results 15 to 20 minutes later makes for a much more reasonable process, albeit one still a long way from implementation.

The NFL is in search of what Jeff Miller, the league's senior vice president of health and safety policy, described as a more "objective" test for traumatic brain injury (TBI). He said the motivation behind the program through which Quanterix won its grants "was to look for better ways to advance the science around diagnoses of concussion, because you know . . . that there is no objective test, that we rely upon experts in the field who do subjective assessments of players."

Miller, who made news a year ago for being the first NFL official to publicly affirm a link between football and the neurodegenerative disease chronic traumatic encephalopathy, or CTE, praised the array of medical personnel and athletic trainers employed on sidelines and up in skyboxes for being "very good at diagnostics." However, he added, "it is subjective, there is no easy test that you can tell whether a player or an athlete, or a member of our military, or a civilian, has suffered a concussion."

In addition, current testing relies to some degree on athletes self-reporting their symptoms, and as one sports-concussions expert told The Post, "if someone is not willing or forthcoming, then you're going to be a little limited there." Blood tests of biomarkers offer a potential means to avoid the conflicts of interest on the part of players, coaches or team physicians that can get in the way of proper medical treatment.

Jonathan Oliver, a professor of kinesiology at Texas Christian University, and his colleagues are studying the school's football team to measure neurofilament light (which is also sometimes rendered as "NF-L" and shall be referred to that way in this article to avoid confusion with the sports league).

For a 2015 study, they took blood samples at specific periods and compared the results between starters, who could be expected to suffer the most damage, and non-starters. Samples were taken in the offseason, before any impacts, then right before two-a-day practices, right after two-a-days, and then every 14 to 21 days until the end of the season.

Oliver's team found that "our non-starters remained flat throughout the season," but the starters' levels of NF-L showed a correlation with impacts, rising by the end of two-a-days, falling during the early portion of the season and "creeping back up" later in conference play. That pattern "is what you'd expect," he said, "because they would get more playing time" as games became tougher and more meaningful.

For that study, Oliver deliberately excluded Horned Frogs (that's what TCU players are called) who had been diagnosed with concussions, because he wanted to "identify at what point players may get to a level that we're seeing elevations in this marker, NF-L, such that they match what somebody who has a concussion looks like." That way, decisions about pulling players from games or prolonging their recovery periods could be at least partly informed by their blood tests, and possibly entirely so if the players in question weren't showing — or, as too often happens, weren't reporting — any symptoms.

Even though a given player "may not be suffering from a concussion, the marker's indicating that, 'Hey, we may have a problem here,'" Oliver said. He noted that being able to look at one or more biomarkers could be all the more useful because "in football players in particular, there's a huge number that go unreported."

Some players are worried that if they report concussions, they will be pulled from games, Oliver said. But, he pointed out, if an athlete suffers a concussion that goes untreated, then suffers another one, "the damage could be much greater."

Hrusovsky agreed that, within the "culture" of football, a player is often "expected to be tough," which can lead to a resistance to leaving the field "because of some subjective test."

"If there's a more objective way to determine if that player has put himself at risk," he added, the emerging science "could play a role in really helping change the culture of the game to make sure that athletes are protected."

Of course, athletes from many more sports than football are at risk of TBI. Colleagues of Oliver's in Sweden published a 2014 study in which they enlisted 288 players from that country's top hockey league. (Oliver also noted that the NFL/NF-L coincidence was largely wasted on his Swedish colleagues.)

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