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Can Technology Repair Memory Loss? New Resource-Backed Breakthroughs Look Promising | New






New brain research at UCSF could one day be used to combat human memory loss, researchers say. (Decade3D/Shutterstock)




Can the biotech industry find a way to repair the human brain from injury and memory loss? Breakthroughs at UCSF backed by Silicon Valley resources may offer the best chance yet.

In a new study that UCSF neurology experts describe as “remarkable” and “striking”, researchers were able to observe that a drug repaired concussions in mice, restoring their memories and repairing brain damage.

One day, the discovery could help treat Alzheimer’s disease and dementia in people, and the research is backed by Google and $3 billion startup Altos Labs.

“It will be exciting to explore next whether these observations also extend to the hippocampus, the region of the brain in which long-term memory consolidation is thought to take place and where equally remarkable healing effects of ISRIB [the drug being tested] have been documented,” the researchers wrote in a preprint of an academic paper that will now be peer-reviewed.

“We’re still pretty far away from any kind of therapeutic use for people,” warns one of the lead authors, neuroscientist Michael Stryker of UCSF’s Department of Physiology. But he admitted the discovery impressed him.

“I was surprised enough to have looked at the data carefully. I’m very happy to see the result,” says Stryker. “It appears that the animal was not injured” after the administration of the drug, “even some time after the concussion”.

There are several reasons to believe that this discovery is not a flash in the pan: First, the drug has been shown to work in several studies. And second, big companies are devoting funds, personnel and new facilities to the development of the drug.

ISRIB (short for Integrated Stress Response Inhibitor) has shown some ability to restore memory for almost a decade. UCSF researchers have previously shown that it can restore memory loss in mice due to trauma or aging. What’s different about this study is that the researchers watched the drug repair the brain of a living animal and learned how it reversed structural damage. Previously, they didn’t know how it worked — or how to apply the drug to other challenges.

“Little is known about the cellular mechanisms responsible for the progression of long-lasting cognitive deficits,” the study says in its introduction, but it has been discovered. “Amazingly, a brief pharmacological treatment… fully reversed the structural changes” in the brain, according to the study.

In other words, the drug wasn’t just about brain chemistry, it was about brain circuitry. The actual cell structure of the brain changed – even with a brief application of the drug weeks after the brain injury.

How could the researchers see this in the tiny mouse heads? The researchers used what is called longitudinal in vivo two-photon fluorescence imaging. It’s quite a mouthful. This means using two lasers to capture 3D brain imaging of live mice.

“We really dove deep into the living brain of an injured animal,” says Susanna Rosi, one of the study’s lead authors and a brain injury expert who recently left UCSF for Altos Labs.

What they saw was “really beautiful,” Rosi says. “We can immediately reverse the effects of brain damage long after. This is what is very remarkable. They saw how the drug works – which is to quickly repair the brain – even long after it has been damaged. And knowing how the drug works could unlock its applications for people.

The other aspect that gives this drug a real chance is that it has a lot of resources. And that’s important.

“The problem with Alzheimer’s disease research is that clinical trials have often failed,” Rosi says. Money is running out, people are moving on, and research is on the sidelines. This is unlikely to happen here. “We certainly have a lot of resources to reach our goal faster than we could in academia,” she says.

Altos Labs, which reportedly invested in Amazon founder Jeff Bezos, hired Rosi and Peter Walter, another study author and ISRIB discoverer, from UCSF. Walter, winner of the prestigious Lasker Prize, worked with Calico Life Sciences, a South San Francisco company owned by Google, on the drug. Today, Altos energizes research.

With this funding and support, development of the drug could be accelerated, Rosi believes. “That’s the beauty of Altos. It’s the best in industry and academia.

Stryker, who did not leave UCSF to join Altos, points out that some of the major lab work was done by students at the university. And not everyone sees the beauty of Altos in the arrangement. The journal Science reported that a new collaboration between UCSF and Altos “allows students to spend the bulk of their Ph.D. training in a biotech start-up. The plan was met with mixed reviews. Some think fast-track drugs shouldn’t be the focus of the Ph.D. programs.

Stryker agrees, however, that “having the resources that Altos apparently has would allow us to move forward much more quickly.” Altos and Google together suggest that “if it fails, it won’t be for lack of resources,” he says.

With 16 million Americans living with cognitive impairment, the promise of these new findings may soon be tested and expanded.

jelder@sfexaminer.com