Two Israeli researchers, one at UC Berkeley and the other at Israel’s Ben-Gurion University, have discovered a mechanism that may be responsible for some of the cognitive decline associated with aging. Not only that, they may have identified how to reverse that process, using a drug developed by a Menlo Park chemist.
“It’s super exciting,” said Daniela Kaufer, professor of integrative biology at UC Berkeley. “It’s the sort of thing you dream to find in your career.”
Kaufer, who came to California to study at Stanford, and longtime Israeli research partner Alon Friedman have been looking for years at the brain-blood barrier, which serves as a filter for the brain. While blood — and what’s in it — circulates around the body fairly freely, the brain is very selective in making sure nothing harmful comes through the barrier.
“In the brain, you don’t want that,” Kaufer said. “It’s the control system.”
Now, in two papers published in December, they’ve presented their research on the way the blood-brain barrier changes with age and how to reverse the negative effects. Kaufer explained that the mechanism that keeps the brain filtering the blood stream can degenerate with age, the case for an estimated 60 percent of people over age 70, she said. “Most people, young people, they don’t have it.”
Kaufer and Friedman had earlier discovered that the blood-brain barrier functioned poorly when someone was under stress or injured, which could account for a host of symptoms associated with head trauma, strokes or epilepsy. Older brains resemble injured brains in many, so it was natural for the scientists to turn their attention to aging, as well.
It’s the sort of thing you dream to find in your career.
About 10 years ago, Kaufer and Friedman found that the most common protein in the blood, albumin, caused inflammation when it leaked into the brain after head trauma. Recently the two infused albumin into the brains of young mice and saw that it made them resemble older mice with cognitive decline. In mice, that means being bad at mazes and other tasks. They then tested senile mice to see whether blocking the mechanism (first through genetic manipulation, then using the drug developed by Barry Hart, a medicinal chemist at pharmaceutical company Virobay) could make their brains function as if they were young again.
“The answer was, yes,” Kaufer said. “You could.”
Conceivably this discovery, culminating decades of work, could lead to therapies for the aging human brain.
Kaufer and Friedman started their collaboration in the mid-’90s in Israel, when Kaufer was a grad student at Hebrew University and Friedman was an army physician. Both had full-time jobs, but in the evenings they did their own research, looking at the impact of stress on the blood-brain barrier. That led to their discovery of the cause of Gulf War syndrome, until then a mysterious condition among soldiers who had been given a drug to protect against chemical weapons. The drug was not supposed to pass the blood-brain barrier, but stress had made it vulnerable, they learned. It was a new concept.
“We’ve almost stumbled into it, to look at this from a different angle,” Kaufer said.
Now that they’ve established the connection between inefficient filtering and cognitive decline, they are thinking about how to use it to help people. One possibility is to use Hart’s drug to prevent the inflammation caused by a leaky blood-brain barrier. To that end, Kaufer, Friedman and Hart have set up a Bay Area company to research the drug further, a necessary step to bring the medicine to market. Although there’s no way to rush a discovery like this into clinical use, Kaufer said she is motivated to make it happen as soon as possible.
“We were getting a lot of emails and calls from very desperate people and family members” as news of their papers hit the media, she said, calling it “heartbreaking.”
Kaufer hopes with the body of research she, Friedman and their collaborators in the field have developed over the past two decades, the drug may reach the first phase of trials within 18 to 24 months.
“That’s optimistic,” she admitted. “But I’m hoping, I’m hoping.”