Jackson Hole, Wyoming — Not your typical geotag for pharmaceutical innovation, Jackson Hole and its most prominent biologist, Paul Cox, may turn decades’ and billions of dollars’ worth of Alzheimer’s research on its head. A new interview in Fortune demonstrates how Cox, working out of a small lab near the region’s famous ski resorts, may be approaching a treatment and preventive protocol for some of the most widespread neurodegenerative diseases. Strikingly, his team is focused not on a lab-borne therapy or expensive pill but on a naturally occurring substance: the amino acid L-serine.
Why Cox started devoting attention to this kind-of random amino acid is a fascinating story in itself. Fluent in more than one Polynesian language, the Harvard PhD moved to Samoa in 1985 with a grant awarded by President Ronald Reagan. There, he began analyzing some practices of the Chamorro, the indigenous people of Guam and the Northern Mariana Islands, whose elders displayed rates of neurodegenerative disease about 100 times higher than people anywhere else on the globe. It’s an astounding statistic, and Cox set out to make some sense of it.
Ultimately, Cox linked the Chamorro’s rates of disease to one of their favorite foods: bat stew. A species of bat called the flying fox, with a wingspan of up to three feet, is a delicacy native to the islands. The bats live on the seeds of cycad trees, which contain such high levels of the neurotoxin BMAA that a single serving of the stew, made from the cycad-eating bats, could wreak brain cell death. There were a few pieces of convincing evidence. Younger Chamorro don’t get sick as earlier generations did—for the elders hunted the bat to extinction. Additionally, Cox and collaborators ultimately found high levels of BMAA in the brains of many patients who had Alzheimer’s in different parts of the globe.
BMAA enters people’s diets through cyanobacteria, ancient algae found in bodies of water large and small all over the globe. Because cyanobacteria proliferated in the pools of water surrounding the roots of cycad trees, the Chamorro people were ingesting extraordinarily high levels of BMAA. Much of the scientific community remains skeptical, but Cox remains attentive to cyanobacteria as likely causes of the BMAA intake that apparently contributes to neurodegeneration.
For the moment, Cox is focused on preventing and fighting the symptoms of neurodegeneration, and that’s where L-serine comes in. His work concluded that BMAA mimics L-serine in order to penetrate protein chains. Sometimes prescribed for chronic fatigue, the FDA has already approved L-serine as a dietary supplement. But recent research by Cox’s team shows how much more the amino acid can do. “It appears to be neuroprotective against all possible protein misfolding,” he says. “It basically turns on a system in our brains that looks for unfolded proteins and is quickly poised to act on them.” In a study Cox performed with the University of Miami, monkeys given both BMAA and L-serine displayed 80–90% fewer neural tangles than those given just BMAA.
But Cox believes his most compelling evidence is what he found on a recent trip to Ogimi, the Japanese city sometimes called the “Village of Longevity,” home to the world’s oldest people and the most centenarians per capita. Collecting the produce and seaweed that make up the diet of an Ogimi resident, Cox was floored to find that it contained 3–4 times more L-serine than the average American diet.
Why This Matters
“We’re all in different fields,” says Larry Brand, a marine biologist who is part of a consortium that Cox leads. “We all present our results and try to connect the dots on everything from causes of algae blooms to medical problems to possible prevention and treatment.”
In the past year alone, more than six big pharma companies watched their hopeful Alzheimer treatments ultimately fail. And over the past few decades, few areas of the life sciences have faced disappointment to the extent that this space has. While pharma admirably pushes forward, it may be a more collaborative, interdisciplinary approach that proves fruitful in the end.
