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Rick Karr is prepared for treatment in Toronto. He was the first Alzheimer’s patient treated with focused ultrasound waves to open the blood-brain barrier — a technique that holds out hope that one day it will help drugs get passed the brain’s protective shield to treat Alzheimer’s disease, the deadly brain cancer glioblastoma and other diseases. | Provided photo

Study suggests way to breach brain’s shield to treat Alzheimer’s, deadly cancer

A handful of Alzheimer’s patients signed up for a bold experiment, allowing scientists to beam sound waves into the brain to temporarily jiggle an opening in its protective shield.

The blood-brain barrier keeps germs and other damaging substances from leaching in through the bloodstream. But it also can block drugs for Alzheimer’s, brain tumors and other neurologic diseases.

Now, researchers are reporting they’ve found hints that technology called focused ultrasound can safely poke holes in that barrier — holes that quickly sealed back up. They say that could be a step toward one day using the non-invasive device to push brain treatments through.

“It’s been a major goal of neuroscience for decades, this idea of a safe and reversible and precise way of breaching the blood-brain barrier,” says Dr. Nir Lipsman, a neurosurgeon at Toronto’s Sunnybrook Health Sciences Centre who led the study. “It’s exciting.”

The findings were presented at the recent Alzheimer’s Association International Conference in Chicago and published in the journal Nature Communications.

This first-step research — conducted in just six people with mild to moderate Alzheimer’s — checked whether patients’ fragile blood vessels could withstand the breach without bleeding or other side effects. It didn’t go so far as to test potential therapies.

More safety testing is needed, but “it’s definitely promising,” says Dr. Eliezer Masliah of the National Institute on Aging, who wasn’t involved with the study. “What is remarkable is that they could do it in a very focused way, they can target a very specific brain region.”

Alzheimer’s isn’t the only target. A similar safety study is underway regarding amyotrophic lateral sclerosis — Lou Gehrig’s disease. And researchers are testing whether the tool helps more chemotherapy reach the right spot in people with a brain tumor called glioblastoma — one of the deadliest cancers.

“We don’t want to broadly open the blood-brain barrier everywhere,” says Dr. Graeme Woodworth of the University of Maryland Medical Center, who will lead a soon-to-begin brain tumor study. “We want to open the blood-brain barrier where we want the treatment to be delivered.”

Scientists have long tried different strategies to overcome the blood-brain barrier but with little success. The brain’s blood vessels are lined with cells that form tight junctions — almost like a zipper. The barrier lets in select, small molecules. Often, treatments for brain diseases are too big to easily pass.

The new approach: Scientists inject microscopic bubbles into the bloodstream. Through an MRI scanner, they aim at a precise brain area. Then, they beam ultrasound waves through a helmet-like device to that particular spot. The pulses of energy make the microbubbles vibrate, loosening those zipper-like junctions. The hope is that medications could slip through.

Within minutes, Lipsman’s team saw a medical dye appear on the Alzheimer’s patients’ brain scans — proof that the barrier opened. A repeat scan the next day showed it was closed again. Patients repeated the procedure a month later.

The study — funded by the nonprofit Focused Ultrasound Foundation — found no serious side effects and no worsening of cognitive function.

“It’s not painful or anything,” says Rick Karr of Everett, Ontario, a retired truck driver and amateur musician who was the study’s first participant.

Karr was diagnosed with Alzheimer’s in 2011. Doctors made clear the study wouldn’t treat his memory problems, but “I feel privileged,” Karr says. “I could help somebody else down the road.”

Brain scans of the first Alzheimer’s patient treated with focused ultrasound to open the blood-brain barrier. A study using the technique suggests that one day it might be possible to get drugs past the barrier to better treat Alzheimer’s disease, the dea

Brain scans of the first Alzheimer’s patient treated with focused ultrasound to open the blood-brain barrier. A study using the technique suggests that one day it might be possible to get drugs past the barrier to better treat Alzheimer’s disease, the deadly brain cancer glioblastoma and other diseases. | Sunnybrook Health Sciences Centre

A French company, CarThera, is testing a different ultrasound technique for brain tumors, using an implant attached to the skull during surgery.

For the non-invasive ultrasound, device maker InSightec has permission from the federal Food and Drug Administration to begin the Maryland tumor trial and a small U.S. Alzheimer’s study.

This time, scientists plan to aim deeper into Alzheimer’s-affected brains to a key memory region, according to the lead researcher, Dr. Ali Rezai of West Virginia University’s Rockefeller Neuroscience Institute. And they’ll measure whether just opening the barrier could help the body clear away the sticky plaques that are a hallmark of Alzheimer’s. Mouse studies — the results of which often differ from what’s later shown to work for humans — suggested that’s a possibility.

The bigger interest by far is in using ultrasound to deliver drugs — if the next-step studies conclude that’s safe to try.

“The blood-brain barrier’s no longer off-limits,” Rezai says.

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