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Claims of Detection Confuse Hunt for Football’s Brain-Trauma Disease

For football fans, there is no time longer than the two weeks, in late January, between the NFL’s conference-championship games and the Super Bowl. It’s a news wasteland, a long pause in the postseason’s frenetic action, and sports reporters scramble to find the slimmest fresh angles to corral their fickle, and hungry, readers.

So you can imagine that a press release sent out by the University of California at Los Angeles just before this year’s Super Bowl, “UCLA Study First to Image Concussion-Related Abnormal Brain Proteins in Retired NFL Players,” got a bit of attention. “PET Scan May Reveal C.T.E. Signs, Study Says,” The New York Times article was headlined; CNN, ESPN, and others published similar reports. A cursory reading of the coverage would have prompted almost anyone to think: Well, this is a problem that’s about solved.

At the end of “A Brain Gone Bad,” my recent article on an attempt at Boston University to detect chronic traumatic encephalopathy in former NFL players, I mention that two research groups have, in fact, developed tracer chemicals for brain scans that bind exclusively to tau, the defective protein at the root of CTE. But neither effort comes from UCLA. How could that be?

Just mentioning the UCLA study to Robert A. Stern, the lead investigator of the Boston University group, prompted a conversational detour when we talked in March. The UCLA study was premature, he said. It cited only a handful of test subjects. It didn’t match the canonical CTE pathology his center had laid out. And at its core, its scans relied on a “dirty” tracer—that is, a chemical that’s less than selective when it comes to binding with brain proteins.

They saw tau, or maybe they didn’t, Stern said. There’s no way of knowing. Despite that uncertainty, the news coverage had peers calling Stern to check on him.

“The UCLA hype was so strong,” Stern said, “that people actually came and said, ‘So is this study over? You’re not going to do it anymore? They’ve found it.’”

The leader of the UCLA effort, Gary W. Small, a professor of psychiatry and biobehavioral sciences at UCLA’s Semel Institute for Neuroscience and Human Behavior, disputes Stern’s characterization. The effort was preliminary but successful enough to warrant publication, he said. Yes, his team used an older tracer, one known to bind to multiple different proteins in the brain. But it displayed a pattern that he had never seen before.

“The overall binding pattern in the retired players we studied,” Small said, “differed from that observed in typical Alzheimer’s dementia, geriatric depression, progressive supranuclear palsy, and other conditions we have studied.”

So who’s right? Let’s take a step back.

In many respects, CTE is similar to Alzheimer’s disease, with one difference: In Alzheimer’s two proteins go awry in the brain, tau and amyloid-beta, while CTE is tied only to tau. Because those defective proteins are invisible in normal scans, scientists have developed molecules that will pass into the brain and bind to the defective proteins. The tracers are then visible in PET scans, gleaming beacons of potential disease.

Small was behind one of the first tracers aimed at Alzheimer’s, a chemical called FDDNP. The molecule first served as a tracer for amyloid-beta, but then researchers discovered it also attached to tau; it wasn’t as selective as they thought. Some scientists believe the tracer binds with a variety of proteins, and there are lingering questions of its utility in diagnosing Alzheimer’s disease.

Given its tau pathology, however, CTE presented a promising new avenue for FDDNP. So along with Bennet Omalu, a pioneer in CTE research and a clinical professor of pathology at the University of California at Davis, Small and his team recruited five former NFL players, age 45 years and older, who had a history of concussions or cognitive problems. The researchers injected the retired players with FDDNP and put them under a PET scanner.

What they saw was surprising, Small said, and called for publication.

“The results were striking,” he said. “The FDDNP binding patterns were clearly different from what we had seen in other conditions and consistent with what had been published in autopsy follow-up studies of CTE. We thought this might increase interest in this area and stimulate other groups to follow this lead.”

Listen closely to Small, read the study, and you’ll see that the researchers also think more work needs to be done before they can say they’ve actually detected CTE in living patients. (Much of the press coverage of the study had a paragraph of caveats to that effect, before galloping onward with the story.) And while Small may have encouraged other researchers to take up his lead, others are, arguably, well ahead of him.

Over the past couple of years, two teams have created tracers for human beings that bind only to tau. One group is based at the University of Melbourne, in Australia, and the other is now part of Eli Lilly and Company, a multinational drug company that will seek to sell the tracer. The teams have published their results, to acclaim, but they have not shouted it from the rooftops. There’s much work to be done.

“This is probably the most exciting thing in the entire field,” said Stern, who hopes to collaborate with the Eli Lilly team, during my visit. “Not just in CTE, but in the whole of neurodegenerative diseases.”

In the end, Stern doesn’t take issue with Small’s effort to find a new application for FDDNP. Though he did not find Small’s study persuasive, that could change as it grows.

No, what really got him going was the presentation, he said. There’s so much desperation out there; people will seize on the slimmest reed of hope. So don’t go saying you’ve found the “holy grail” of CTE diagnosis, as one of Small’s co-authors did in the UCLA press release, until you’re certain you’ve got it. Don’t do false hope.

“We’re not going to publish things prematurely,” Stern said. “Or claim that we have answers before we have answers.”

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