Alzheimer’s study breaches brain barrier
Alzheimer’s patients have allowed scientists to beam soundwaves into the brain to temporarily jiggle an opening in its protective shield as part of a bold experiment. The so-called blood-brain barrier prevents germs and other damaging substances from leaching in through the bloodstream — but it can block drugs for Alzheimer’s, brain tumours and other neurological diseases.
Canadian researchers on Wednesday reported early hints that technology called focused ultrasound can safely poke holes in the barrier — holes that quickly sealed back up — 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,” said 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 Alzheimer’s Association International Conference in Chicago and published in Nature Communications. The findings were among several announced at the conference, including a study that found lowering blood pressure can curb the disease.
The focused ultrasound research, conducted in six people with mild to moderate Alzheimer’s, checked if patients’ fragile blood vessels could withstand the breach without bleeding or other side-effects. It did not test potential therapies.
More safety testing is needed, but “it’s definitely promising,” said 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 in Lou Gehrig’s disease. Researchers are also testing if the tool helps more chemotherapy reach the right spot in people with a deadly brain tumour called glioblastoma.
“We don’t want to broadly open the blood-brain barrier everywhere. We want to open the blood-brain barrier where we want the treatment to be delivered,” said Dr. Graeme Woodworth of the Baltimorebased University of Maryland Medical Center, who is about to lead a brain-tumour study.
Scientists have long tried strategies to overcome the blood-brain barrier, 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 is for scientists to 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 spot. The pulses of energy make the microbubbles vibrate, loosening those zipper-like junctions in the hope that medications can slip inside.
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.
Researchers reported no serious sideeffects, and no worsening of cognitive function. The study was funded by the nonprofit Focused Ultrasound Foundation.
“It’s not painful or anything,” said Rick Karr of Everett, Ont., the study’s first participant. A retired truck driver and amateur musician, Karr was found to have Alzheimer’s in 2011. Doctors made clear the study wouldn’t treat his memory problems, but “I feel privileged,” Karr said. “I could help somebody else down the road.”
A French company, CarThera, is testing a different ultrasound technique for brain tumours, using an implant attached to the skull during surgery.
For the non-invasive ultrasound, device maker InSightec has U.S. Food and Drug Administration permission to begin the Maryland tumour trial and a small U.S. Alzheimer’s study.
This time, scientists will aim deeper into Alzheimer’s-affected brains to a key memory region, said lead researcher Dr. Ali Rezai of West Virginia University’s Rockefeller Neuroscience Institute. They will measure if simply opening the barrier could help the body clear away sticky plaques that are a hallmark of Alzheimer’s, after studies on mice suggested that is a possibility.
But by far the bigger interest is in using ultrasound to deliver drugs — if the nextstep studies conclude it’s safe to try.
“The blood-brain barrier’s no longer offlimits,” Rezai said.
Another study announced at the conference found that lowering blood pressure more than usually recommended not only helps prevent heart problems, it cuts the risk of mental decline that often leads to Alzheimer’s disease.
It’s the first time a single step has been clearly shown to help prevent the disease.
In the study, people treated to a top blood-pressure reading of 120 instead of 140 were 19 per cent less likely to develop mild cognitive impairment. They also had fewer signs of damage on brain scans, and there was a possible trend toward fewer cases of dementia.
“This is a big breakthrough,” said Dr. Jeff Williamson of Wake Forest Baptist Medical Center in North Carolina.
“It’s more important than ever to work with your physician to ensure that you have good blood pressure control.”
He led the study and gave the results Wednesday at the Alzheimer’s conference. The results are expected to be published this year.
Independent experts cheered the news. “We have long known that high blood pressure is bad for your heart. Now we’re also learning it’s bad for your brain,” said James Hendrix, director of global science initiatives for the Chicago-based Alzheimer’s Association.
High pressure can damage blood vessels and has long been linked to a higher risk of dementia. But it has not been known if lowering pressure would reduce the risk or by how much.
The U.S. federally funded study was designed to test this in the most rigorous way. The study involved more than 9,300 people with high pressure. Half got two medicines, on average, to get their top reading below 140.
The rest got three drugs, on average, and aimed for 120. During the study, the top pressure averaged 121 in the intensive-treatment group and 135 in the other group.
The study was stopped in 2015, nearly two years early, when it became clear that lower pressure helped to prevent heart problems and deaths. But tests of thinking skills continued for two more years, and the new results were disclosed on Wednesday.
Researchers saw a 19 per cent lower risk of mild cognitive impairment in the intensive-treatment group — 285 cases versus 348 in the higher pressure group. About half of people with MCI develop dementia over the next five years.