In one of the biggest breakthroughs to date, researchers from Boston University School of Medicine have discovered a key biomarker for chronic traumatic encephalopathy that they hope marks the first step toward being able to diagnose and ultimately treat the neurodegenerative disease in a living football player.
Dr. Ann McKee, the neuropathologist credited with some of the most high-profile CTE diagnoses, said she was buoyed by the recent discovery, calling it "the first ray of hope" in a years-long effort to understand the disease.
"To me, it feels like maybe now we can start going in the other direction," she said. "We've been going down, and everything has just gotten more and more depressing. And now it's like, 'Yeah, we're going to actually find some answers here.'"
In a new study published Tuesday in the journal PLOS ONE, researchers from BU and the VA Boston Healthcare System studied the brains of 23 former football players who were diagnosed with CTE, in addition to those of 50 non-athletes who suffered from Alzheimer's disease and 18 non-athlete controls. They found significantly elevated levels of a protein related to inflammation called CCL11 in the group of ex-players compared with the non-athletes. The levels were even higher in those who played the game longer.
She cautioned that a lot more research is needed. The BU findings are preliminary and have to be validated. But researchers are hopeful that if an elevated biomarker in a living person might indicate the presence of CTE, research into prevention and treatment of the disease can begin to move forward.
"It's a unique disease, and it's going to have unique proteins that are modified in this disease, and this is the first indication that we've found one of the unique proteins," said McKee, the director of BU's CTE Center and senior author of the new study.
Researchers have been studying the disease in earnest since Dr. Bennet Omalu first published a paper in the journal Neurosurgery 12 years ago called "Chronic Traumatic Encephalopathy in a National Football League Player." While leading experts agree the disease is linked to the repetitive hits suffered on the football field, it can be diagnosed only after a player has died. That has meant that many former players who suffered late in their lives from the effects of CTE never knew for certain they had the disease. McKee alone has made post-mortem CTE diagnoses on ex-players such as tight end Aaron Hernandez, who was serving a life sentence in prison when he killed himself in April.
"This has really been our purpose: to give back to future generations," she said. "It wasn't just to categorize the disease and to find what these individuals had when they died. It's really to understand CTE at the molecular and biochemical level, so we can figure out ways to detect it and more importantly, treat it."
Because neuropathologists can't diagnose CTE in a living person, the study was limited to post-mortem brain tissue and samples of cerebrospinal fluid, "but it gives us clues that we might be able to detect it in living people," McKee said.
Of the 23 brains studied, 19 belonged to professional football players — including 18 who played in the NFL — and four others who reached the college level. The age range was 25 to 87 with a mean age of 62. The early findings do not necessarily allow researchers to determine how early they eventually might be able to detect the disease in a living person, McKee said. Of the samples studied, one came from a 49-year-old ex-player and another from a 53-year-old. Both of those subjects were diagnosed with Stage II (out of four stages) CTE.
"Those are on the younger side and had relatively earlier CTE and we still found this elevation, so that's really optimistic for the future," she said. "Obviously, now we'll go back and look at very early and young individuals and see if this is a marker of very early stage CTE."
While she is hopeful future studies support and expand on the initial findings, McKee said the new study should illustrate enough to silence any lingering skeptics who might doubt CTE's existence. The unique biomarker should help distinguish the disease from Alzheimer's disease, which often presents similar symptoms.
"I've been frustrated for years that we keep discussing or debating whether or not this disease exists, whether or not it's unique, whether it's simply aging," she said. "This is the first demonstration that shows it's clearly not aging. It is a distinct disease, and we're going to exploit the uniqueness of this disease to find treatment."
Saying the new findings are "certainly important," an NFL spokesman noted that more research is needed and the league has allocated $40 million toward medical research.
"Research around CTE must continue to move forward and fill in the gaps that remain around this important issue," NFL spokesman Brian McCarthy said in a statement. "The NFL is committed to encouraging and supporting scientific research related to the diagnosis and treatment of concussion and associated conditions, including CTE."
McKee hopes future studies might be able to show the biomarker can be found in blood tests and perhaps show whether elevated CCL11 levels reveal anything about the severity of a subject's disease. While the research will continue, McKee and her team are hopeful this latest discovery finally cracks open a door they have been staring at for a dozen years.
"This was the first finding of a really unique component in this disease compared to others and compared to controls, so, yeah, it's a eureka moment, but we don't think it's the end," she said. "We think it's the beginning."