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◀ KUN PING LU, M.D., Ph.D., and XIAO ZHEN ZHOU,
M.D., are creating an antibody that could help
prevent brain-impact injuries.
tracks of matter that transfer impulses that have received a portion of a $14.7 million grant
between neurons. Their work suggested from the league. Part of the grant, awarded in Novem-
that when Pin1 levels are too low, the ber 2018, will also fund an epidemiological study that
tau protein deforms. This misshapen will closely track the changing health, especially in the
version of tau is called cis tau—“the bad brain, of as many as 2,500 retired NFL players as they
guy,” Dr. Lu says. When too much cis move through the rest of their lives. Bill Meehan, M.D.,
tau is present in the brain, axons will a brain researcher at Boston Children’s Hospital, who
break down and collapse. This, accord- is overseeing the studies, says his group will then select
ing to his theory, contributes to Alzheimer’s disease. whichever of the four therapies “look most promising in the lab” and bring
In her earlier work on Alzheimer’s, Dr. Zhou had them into human clinical trials. The idea is to enroll those same retired NFL
created a kind of antibody that could detect only the players as the trials’ subjects. Dr. Meehan will not assess the odds of the four
odd shape of cis tau. Using this antibody, she, her therapies’ success. “But I will say this: The cis tau antibody is very, very far
husband, and their colleagues observed that cis tau along. I think it’s probably one of the most promising therapies out there.”
levels in the axons of mouse and human brains escalate Dr. Lu and Dr. Zhou would also like to use the NFL study to understand
sharply in the hours after a single instance of head why many football players who have endured long careers taking repeated
trauma—whether a mild concussion given to a mouse head blows never develop CTE. They believe such people may possess a
or a fatal injury such as in a car accident—which they naturally occurring version of their cis antibody, an autoantibody. In other
discovered by dissecting victims’ postmortem brains. words, they believe there are people who are immune to CTE. To fi nd out, the
After repeated mild blows similar to those in sports- couple want to examine the retired NFL players enrolled in Dr. Meehan’s
related injuries, or even a single severe head injury or study. If they fi nd an autoantibody, they’ll clone it.
high-pressure blast exposure, as in a traffi c collision or Already, Dr. Lu says, “we’re in process of identifying” such players. His
a bomb blast, however, the cis tau levels did not return voice rises with excitement as he says this. He laughs. But then Dr. Zhou
to normal. Through a series of lab studies, the doctors shuts him up. Say no more, her body language commands. The stakes are too
would eventually show the antibody eradicating the high, the work preliminary. “It’s too early!” she says.
bad guy—results that were published in Nature in
2015. Molecularly, behaviorally, cognitively, mice with
the rodent equivalent of CTE had been cured.
Kun Ping Lu is a tiny man with graying hair who is Dr. Lu told me, “If a player gets a big hit or many small hits, I would give
quick to laugh. Xiao Zhen Zhou is a tiny woman with him a dose ofthe antibody.If it’s caught early, then maybe their sport will
graying hair who is quick to laugh. On a day in July, not be afraid anymore.” But should any treatment for concussion or CTE
deep inside Beth Israel Deaconess Medical Center, ever reach the market, some in the world of concussion science and therapy
one of the giant Boston research hospitals affi liated worry that it might cause other sorts of problems.
with Harvard, the husband-and-wife team, both in “In theory, if it helps the patient recover and doesn’t put them at more
their 50s, showed me around their cluttered lab, with risk, it’s a good thing,” says Nowinski of the Concussion Legacy Founda-
its warren of benches, its white-coated young re- tion. “The obvious concern would be: Does it mask symptoms? Does it
searchers standing at the benches, its computerized improve the brain in some ways but not enough to shorten the safe return-
time-lapse microscope-imaging systems, its in-vitro to-play window? It has an obvious risk of being abused in a sports setting.”
neuron-stretching contraptions, its comically gigan- The concern is part clinical and part cultural. Would a concussion drug
tic beakers, its cryogenic vats of living antibody- or even a CTE cure preserve not only the sport of American football but also
producing cells frozen at –195 degrees Celsius. its violence? If such treatments exist, do you give the sport license to re-up
Among their most important tasks now is to its commitment to brutality? As Jay Clugston, M.D., a team physician at
humanize the antibody—to create a version that can the University of Florida, puts it to me, a player might say to himself, “It
be injected safely into human beings. Dr. Zhou is in doesn’t matter, man. I’ll lower my head, use my head. I know I can clear up
charge of the process. It is incredibly painstaking any damage I accrue.”
work, almost artisanal. Generations of cell cultures “As a team physician,” continues Dr. Clugston, who has advised Preva-
must be nurtured and evolved into further generations cus, “I gotta say, we’d much rather prevent concussion than we would treat
with antibody protein sequences ever more human- it. If the injury is going to occur, then fi nding a way to treat it is very import-
like. It is also costly. But no problem. They have NIH/ ant. But I feel like . . . why are we doing this activity if you have to take a drug
National Institute of Neurological Disorders and to protect your brain ahead of time?”
Stroke funding. They’ve also cofounded a start-up, Football’s concussion predicament has long been on VanLandingham’s
called Pinteon Therapeutics, with the goal of eventu- mind. “You have to fi rst ask yourself: Is football gonna go away if there’s
ally commercializing the antibody. Working in parallel not a treatment? And the answer most likely is no,” he says. But he also
with but separate from Dr. Lu and Dr. Zhou, Pinteon’s once told me, speaking of the Prevacus drug, “I hope one day that this helps
scientists recently completed the humanization of one keep football . . . as pristine as possible. I love to see a big hit. I think football
variant of the antibody. Pinteon started Phase 1 trials should be violent. If there wasn’t football, I’d be miserable. It is my favorite
in humans for that variant in September. thing on this earth.”
Dr. Lu and Dr. Zhou have also been helped along by Joel Haskell (Lu and Zhou)
money from the NFL. Their cis tau antibody is one of SCOTT EDEN is a reporter who often writes about the intersection of sports and
four potential treatments for TBI-linked ailments science. His last story for Men’s Health was about the opioid crisis.
110 December 2019 / MEN’S HEALTH
